PodNet, a protein-protein interaction network of the podocyte.

PubMed

Warsow, Gregor; Endlich, Nicole; Schordan, Eric; Schordan, Sandra; Chilukoti, Ravi K; Homuth, Georg; Moeller, Marcus J; Fuellen, Georg; Endlich, Karlhans

2013-07-01

Interactions between proteins crucially determine cellular structure and function. Differential analysis of the interactome may help elucidate molecular mechanisms during disease development; however, this analysis necessitates mapping of expression data on protein-protein interaction networks. These networks do not exist for the podocyte; therefore, we built PodNet, a literature-based mouse podocyte network in Cytoscape format. Using database protein-protein interactions, we expanded PodNet to XPodNet with enhanced connectivity. In order to test the performance of XPodNet in differential interactome analysis, we examined podocyte developmental differentiation and the effect of cell culture. Transcriptomes of podocytes in 10 different states were mapped on XPodNet and analyzed with the Cytoscape plugin ExprEssence, based on the law of mass action. Interactions between slit diaphragm proteins are most significantly upregulated during podocyte development and most significantly downregulated in culture. On the other hand, our analysis revealed that interactions lost during podocyte differentiation are not regained in culture, suggesting a loss rather than a reversal of differentiation for podocytes in culture. Thus, we have developed PodNet as a valuable tool for differential interactome analysis in podocytes, and we have identified established and unexplored regulated interactions in developing and cultured podocytes.

Network Analysis: A Novel Approach to Understand Suicidal Behaviour

PubMed Central

de Beurs, Derek

2017-01-01

Although suicide is a major public health issue worldwide, we understand little of the onset and development of suicidal behaviour. Suicidal behaviour is argued to be the end result of the complex interaction between psychological, social and biological factors. Epidemiological studies resulted in a range of risk factors for suicidal behaviour, but we do not yet understand how their interaction increases the risk for suicidal behaviour. A new approach called network analysis can help us better understand this process as it allows us to visualize and quantify the complex association between many different symptoms or risk factors. A network analysis of data containing information on suicidal patients can help us understand how risk factors interact and how their interaction is related to suicidal thoughts and behaviour. A network perspective has been successfully applied to the field of depression and psychosis, but not yet to the field of suicidology. In this theoretical article, I will introduce the concept of network analysis to the field of suicide prevention, and offer directions for future applications and studies.

Enabling Community Through Social Media

PubMed Central

Haythornthwaite, Caroline

2013-01-01

Background Social network analysis provides a perspective and method for inquiring into the structures that comprise online groups and communities. Traces from interaction via social media provide the opportunity for understanding how a community is formed and maintained online. Objective The paper aims to demonstrate how social network analysis provides a vocabulary and set of techniques for examining interaction patterns via social media. Using the case of the #hcsmca online discussion forum, this paper highlights what has been and can be gained by approaching online community from a social network perspective, as well as providing an inside look at the structure of the #hcsmca community. Methods Social network analysis was used to examine structures in a 1-month sample of Twitter messages with the hashtag #hcsmca (3871 tweets, 486 unique posters), which is the tag associated with the social media–supported group Health Care Social Media Canada. Network connections were considered present if the individual was mentioned, replied to, or had a post retweeted. Results Network analyses revealed patterns of interaction that characterized the community as comprising one component, with a set of core participants prominent in the network due to their connections with others. Analysis showed the social media health content providers were the most influential group based on in-degree centrality. However, there was no preferential attachment among people in the same professional group, indicating that the formation of connections among community members was not constrained by professional status. Conclusions Network analysis and visualizations provide techniques and a vocabulary for understanding online interaction, as well as insights that can help in understanding what, and who, comprises and sustains a network, and whether community emerges from a network of online interactions. PMID:24176835

Integrated network capacity analysis for freight railroads.

DOT National Transportation Integrated Search

2016-02-23

Rail network capacity analysis should consider all network infrastructures in an integrated way, with the challenges of the nonlinear relationships at each network element, a link or a node, and complexity of the interaction between various network e...

Human Dopamine Receptors Interaction Network (DRIN): a systems biology perspective on topology, stability and functionality of the network.

PubMed

Podder, Avijit; Jatana, Nidhi; Latha, N

2014-09-21

Dopamine receptors (DR) are one of the major neurotransmitter receptors present in human brain. Malfunctioning of these receptors is well established to trigger many neurological and psychiatric disorders. Taking into consideration that proteins function collectively in a network for most of the biological processes, the present study is aimed to depict the interactions between all dopamine receptors following a systems biology approach. To capture comprehensive interactions of candidate proteins associated with human dopamine receptors, we performed a protein-protein interaction network (PPIN) analysis of all five receptors and their protein partners by mapping them into human interactome and constructed a human Dopamine Receptors Interaction Network (DRIN). We explored the topology of dopamine receptors as molecular network, revealing their characteristics and the role of central network elements. More to the point, a sub-network analysis was done to determine major functional clusters in human DRIN that govern key neurological pathways. Besides, interacting proteins in a pathway were characterized and prioritized based on their affinity for utmost drug molecules. The vulnerability of different networks to the dysfunction of diverse combination of components was estimated under random and direct attack scenarios. To the best of our knowledge, the current study is unique to put all five dopamine receptors together in a common interaction network and to understand the functionality of interacting proteins collectively. Our study pinpointed distinctive topological and functional properties of human dopamine receptors that have helped in identifying potential therapeutic drug targets in the dopamine interaction network. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comprehensive curation and analysis of global interaction networks in Saccharomyces cerevisiae

PubMed Central

Reguly, Teresa; Breitkreutz, Ashton; Boucher, Lorrie; Breitkreutz, Bobby-Joe; Hon, Gary C; Myers, Chad L; Parsons, Ainslie; Friesen, Helena; Oughtred, Rose; Tong, Amy; Stark, Chris; Ho, Yuen; Botstein, David; Andrews, Brenda; Boone, Charles; Troyanskya, Olga G; Ideker, Trey; Dolinski, Kara; Batada, Nizar N; Tyers, Mike

2006-01-01

Background The study of complex biological networks and prediction of gene function has been enabled by high-throughput (HTP) methods for detection of genetic and protein interactions. Sparse coverage in HTP datasets may, however, distort network properties and confound predictions. Although a vast number of well substantiated interactions are recorded in the scientific literature, these data have not yet been distilled into networks that enable system-level inference. Results We describe here a comprehensive database of genetic and protein interactions, and associated experimental evidence, for the budding yeast Saccharomyces cerevisiae, as manually curated from over 31,793 abstracts and online publications. This literature-curated (LC) dataset contains 33,311 interactions, on the order of all extant HTP datasets combined. Surprisingly, HTP protein-interaction datasets currently achieve only around 14% coverage of the interactions in the literature. The LC network nevertheless shares attributes with HTP networks, including scale-free connectivity and correlations between interactions, abundance, localization, and expression. We find that essential genes or proteins are enriched for interactions with other essential genes or proteins, suggesting that the global network may be functionally unified. This interconnectivity is supported by a substantial overlap of protein and genetic interactions in the LC dataset. We show that the LC dataset considerably improves the predictive power of network-analysis approaches. The full LC dataset is available at the BioGRID () and SGD () databases. Conclusion Comprehensive datasets of biological interactions derived from the primary literature provide critical benchmarks for HTP methods, augment functional prediction, and reveal system-level attributes of biological networks. PMID:16762047

Bacterial molecular networks: bridging the gap between functional genomics and dynamical modelling.

PubMed

van Helden, Jacques; Toussaint, Ariane; Thieffry, Denis

2012-01-01

This introductory review synthesizes the contents of the volume Bacterial Molecular Networks of the series Methods in Molecular Biology. This volume gathers 9 reviews and 16 method chapters describing computational protocols for the analysis of metabolic pathways, protein interaction networks, and regulatory networks. Each protocol is documented by concrete case studies dedicated to model bacteria or interacting populations. Altogether, the chapters provide a representative overview of state-of-the-art methods for data integration and retrieval, network visualization, graph analysis, and dynamical modelling.

Analysis of Context Dependence in Social Interaction Networks of a Massively Multiplayer Online Role-Playing Game

PubMed Central

Son, Seokshin; Kang, Ah Reum; Kim, Hyun-chul; Kwon, Taekyoung; Park, Juyong; Kim, Huy Kang

2012-01-01

Rapid advances in modern computing and information technology have enabled millions of people to interact online via various social network and gaming services. The widespread adoption of such online services have made possible analysis of large-scale archival data containing detailed human interactions, presenting a very promising opportunity to understand the rich and complex human behavior. In collaboration with a leading global provider of Massively Multiplayer Online Role-Playing Games (MMORPGs), here we present a network science-based analysis of the interplay between distinct types of user interaction networks in the virtual world. We find that their properties depend critically on the nature of the context-interdependence of the interactions, highlighting the complex and multilayered nature of human interactions, a robust understanding of which we believe may prove instrumental in the designing of more realistic future virtual arenas as well as provide novel insights to the science of collective human behavior. PMID:22496771

Influences of brain development and ageing on cortical interactive networks.

PubMed

Zhu, Chengyu; Guo, Xiaoli; Jin, Zheng; Sun, Junfeng; Qiu, Yihong; Zhu, Yisheng; Tong, Shanbao

2011-02-01

To study the effect of brain development and ageing on the pattern of cortical interactive networks. By causality analysis of multichannel electroencephalograph (EEG) with partial directed coherence (PDC), we investigated the different neural networks involved in the whole cortex as well as the anterior and posterior areas in three age groups, i.e., children (0-10 years), mid-aged adults (26-38 years) and the elderly (56-80 years). By comparing the cortical interactive networks in different age groups, the following findings were concluded: (1) the cortical interactive network in the right hemisphere develops earlier than its left counterpart in the development stage; (2) the cortical interactive network of anterior cortex, especially at C3 and F3, is demonstrated to undergo far more extensive changes, compared with the posterior area during brain development and ageing; (3) the asymmetry of the cortical interactive networks declines during ageing with more loss of connectivity in the left frontal and central areas. The age-related variation of cortical interactive networks from resting EEG provides new insights into brain development and ageing. Our findings demonstrated that the PDC analysis of EEG is a powerful approach for characterizing the cortical functional connectivity during brain development and ageing. Copyright © 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Non-criticality of interaction network over system's crises: A percolation analysis.

PubMed

Shirazi, Amir Hossein; Saberi, Abbas Ali; Hosseiny, Ali; Amirzadeh, Ehsan; Toranj Simin, Pourya

2017-11-20

Extraction of interaction networks from multi-variate time-series is one of the topics of broad interest in complex systems. Although this method has a wide range of applications, most of the previous analyses have focused on the pairwise relations. Here we establish the potential of such a method to elicit aggregated behavior of the system by making a connection with the concepts from percolation theory. We study the dynamical interaction networks of a financial market extracted from the correlation network of indices, and build a weighted network. In correspondence with the percolation model, we find that away from financial crises the interaction network behaves like a critical random network of Erdős-Rényi, while close to a financial crisis, our model deviates from the critical random network and behaves differently at different size scales. We perform further analysis to clarify that our observation is not a simple consequence of the growth in correlations over the crises.

atBioNet--an integrated network analysis tool for genomics and biomarker discovery.

PubMed

Ding, Yijun; Chen, Minjun; Liu, Zhichao; Ding, Don; Ye, Yanbin; Zhang, Min; Kelly, Reagan; Guo, Li; Su, Zhenqiang; Harris, Stephen C; Qian, Feng; Ge, Weigong; Fang, Hong; Xu, Xiaowei; Tong, Weida

2012-07-20

Large amounts of mammalian protein-protein interaction (PPI) data have been generated and are available for public use. From a systems biology perspective, Proteins/genes interactions encode the key mechanisms distinguishing disease and health, and such mechanisms can be uncovered through network analysis. An effective network analysis tool should integrate different content-specific PPI databases into a comprehensive network format with a user-friendly platform to identify key functional modules/pathways and the underlying mechanisms of disease and toxicity. atBioNet integrates seven publicly available PPI databases into a network-specific knowledge base. Knowledge expansion is achieved by expanding a user supplied proteins/genes list with interactions from its integrated PPI network. The statistically significant functional modules are determined by applying a fast network-clustering algorithm (SCAN: a Structural Clustering Algorithm for Networks). The functional modules can be visualized either separately or together in the context of the whole network. Integration of pathway information enables enrichment analysis and assessment of the biological function of modules. Three case studies are presented using publicly available disease gene signatures as a basis to discover new biomarkers for acute leukemia, systemic lupus erythematosus, and breast cancer. The results demonstrated that atBioNet can not only identify functional modules and pathways related to the studied diseases, but this information can also be used to hypothesize novel biomarkers for future analysis. atBioNet is a free web-based network analysis tool that provides a systematic insight into proteins/genes interactions through examining significant functional modules. The identified functional modules are useful for determining underlying mechanisms of disease and biomarker discovery. It can be accessed at: http://www.fda.gov/ScienceResearch/BioinformaticsTools/ucm285284.htm.

Enhancing the Functional Content of Eukaryotic Protein Interaction Networks

PubMed Central

Pandey, Gaurav; Arora, Sonali; Manocha, Sahil; Whalen, Sean

2014-01-01

Protein interaction networks are a promising type of data for studying complex biological systems. However, despite the rich information embedded in these networks, these networks face important data quality challenges of noise and incompleteness that adversely affect the results obtained from their analysis. Here, we apply a robust measure of local network structure called common neighborhood similarity (CNS) to address these challenges. Although several CNS measures have been proposed in the literature, an understanding of their relative efficacies for the analysis of interaction networks has been lacking. We follow the framework of graph transformation to convert the given interaction network into a transformed network corresponding to a variety of CNS measures evaluated. The effectiveness of each measure is then estimated by comparing the quality of protein function predictions obtained from its corresponding transformed network with those from the original network. Using a large set of human and fly protein interactions, and a set of over GO terms for both, we find that several of the transformed networks produce more accurate predictions than those obtained from the original network. In particular, the measure and other continuous CNS measures perform well this task, especially for large networks. Further investigation reveals that the two major factors contributing to this improvement are the abilities of CNS measures to prune out noisy edges and enhance functional coherence in the transformed networks. PMID:25275489

Dynamic Network-Based Epistasis Analysis: Boolean Examples

PubMed Central

Azpeitia, Eugenio; Benítez, Mariana; Padilla-Longoria, Pablo; Espinosa-Soto, Carlos; Alvarez-Buylla, Elena R.

2011-01-01

In this article we focus on how the hierarchical and single-path assumptions of epistasis analysis can bias the inference of gene regulatory networks. Here we emphasize the critical importance of dynamic analyses, and specifically illustrate the use of Boolean network models. Epistasis in a broad sense refers to gene interactions, however, as originally proposed by Bateson, epistasis is defined as the blocking of a particular allelic effect due to the effect of another allele at a different locus (herein, classical epistasis). Classical epistasis analysis has proven powerful and useful, allowing researchers to infer and assign directionality to gene interactions. As larger data sets are becoming available, the analysis of classical epistasis is being complemented with computer science tools and system biology approaches. We show that when the hierarchical and single-path assumptions are not met in classical epistasis analysis, the access to relevant information and the correct inference of gene interaction topologies is hindered, and it becomes necessary to consider the temporal dynamics of gene interactions. The use of dynamical networks can overcome these limitations. We particularly focus on the use of Boolean networks that, like classical epistasis analysis, relies on logical formalisms, and hence can complement classical epistasis analysis and relax its assumptions. We develop a couple of theoretical examples and analyze them from a dynamic Boolean network model perspective. Boolean networks could help to guide additional experiments and discern among alternative regulatory schemes that would be impossible or difficult to infer without the elimination of these assumption from the classical epistasis analysis. We also use examples from the literature to show how a Boolean network-based approach has resolved ambiguities and guided epistasis analysis. Our article complements previous accounts, not only by focusing on the implications of the hierarchical and single-path assumption, but also by demonstrating the importance of considering temporal dynamics, and specifically introducing the usefulness of Boolean network models and also reviewing some key properties of network approaches. PMID:22645556

Coevolution analysis of Hepatitis C virus genome to identify the structural and functional dependency network of viral proteins

NASA Astrophysics Data System (ADS)

Champeimont, Raphaël; Laine, Elodie; Hu, Shuang-Wei; Penin, Francois; Carbone, Alessandra

2016-05-01

A novel computational approach of coevolution analysis allowed us to reconstruct the protein-protein interaction network of the Hepatitis C Virus (HCV) at the residue resolution. For the first time, coevolution analysis of an entire viral genome was realized, based on a limited set of protein sequences with high sequence identity within genotypes. The identified coevolving residues constitute highly relevant predictions of protein-protein interactions for further experimental identification of HCV protein complexes. The method can be used to analyse other viral genomes and to predict the associated protein interaction networks.

Network analysis shining light on parasite ecology and diversity.

PubMed

Poulin, Robert

2010-10-01

The vast number of species making up natural communities, and the myriad interactions among them, pose great difficulties for the study of community structure, dynamics and stability. Borrowed from other fields, network analysis is making great inroads in community ecology and is only now being applied to host-parasite interactions. It allows a complex system to be examined in its entirety, as opposed to one or a few components at a time. This review explores what network analysis is and how it can be used to investigate parasite ecology. It also summarizes the first findings to emerge from network analyses of host-parasite interactions and identifies promising future directions made possible by this approach. Copyright © 2010 Elsevier Ltd. All rights reserved.

Computational Modeling of Allosteric Regulation in the Hsp90 Chaperones: A Statistical Ensemble Analysis of Protein Structure Networks and Allosteric Communications

PubMed Central

Blacklock, Kristin; Verkhivker, Gennady M.

2014-01-01

A fundamental role of the Hsp90 chaperone in regulating functional activity of diverse protein clients is essential for the integrity of signaling networks. In this work we have combined biophysical simulations of the Hsp90 crystal structures with the protein structure network analysis to characterize the statistical ensemble of allosteric interaction networks and communication pathways in the Hsp90 chaperones. We have found that principal structurally stable communities could be preserved during dynamic changes in the conformational ensemble. The dominant contribution of the inter-domain rigidity to the interaction networks has emerged as a common factor responsible for the thermodynamic stability of the active chaperone form during the ATPase cycle. Structural stability analysis using force constant profiling of the inter-residue fluctuation distances has identified a network of conserved structurally rigid residues that could serve as global mediating sites of allosteric communication. Mapping of the conformational landscape with the network centrality parameters has demonstrated that stable communities and mediating residues may act concertedly with the shifts in the conformational equilibrium and could describe the majority of functionally significant chaperone residues. The network analysis has revealed a relationship between structural stability, global centrality and functional significance of hotspot residues involved in chaperone regulation. We have found that allosteric interactions in the Hsp90 chaperone may be mediated by modules of structurally stable residues that display high betweenness in the global interaction network. The results of this study have suggested that allosteric interactions in the Hsp90 chaperone may operate via a mechanism that combines rapid and efficient communication by a single optimal pathway of structurally rigid residues and more robust signal transmission using an ensemble of suboptimal multiple communication routes. This may be a universal requirement encoded in protein structures to balance the inherent tension between resilience and efficiency of the residue interaction networks. PMID:24922508

Computational modeling of allosteric regulation in the hsp90 chaperones: a statistical ensemble analysis of protein structure networks and allosteric communications.

PubMed

Blacklock, Kristin; Verkhivker, Gennady M

2014-06-01

A fundamental role of the Hsp90 chaperone in regulating functional activity of diverse protein clients is essential for the integrity of signaling networks. In this work we have combined biophysical simulations of the Hsp90 crystal structures with the protein structure network analysis to characterize the statistical ensemble of allosteric interaction networks and communication pathways in the Hsp90 chaperones. We have found that principal structurally stable communities could be preserved during dynamic changes in the conformational ensemble. The dominant contribution of the inter-domain rigidity to the interaction networks has emerged as a common factor responsible for the thermodynamic stability of the active chaperone form during the ATPase cycle. Structural stability analysis using force constant profiling of the inter-residue fluctuation distances has identified a network of conserved structurally rigid residues that could serve as global mediating sites of allosteric communication. Mapping of the conformational landscape with the network centrality parameters has demonstrated that stable communities and mediating residues may act concertedly with the shifts in the conformational equilibrium and could describe the majority of functionally significant chaperone residues. The network analysis has revealed a relationship between structural stability, global centrality and functional significance of hotspot residues involved in chaperone regulation. We have found that allosteric interactions in the Hsp90 chaperone may be mediated by modules of structurally stable residues that display high betweenness in the global interaction network. The results of this study have suggested that allosteric interactions in the Hsp90 chaperone may operate via a mechanism that combines rapid and efficient communication by a single optimal pathway of structurally rigid residues and more robust signal transmission using an ensemble of suboptimal multiple communication routes. This may be a universal requirement encoded in protein structures to balance the inherent tension between resilience and efficiency of the residue interaction networks.

Computational Framework for Analysis of Prey–Prey Associations in Interaction Proteomics Identifies Novel Human Protein–Protein Interactions and Networks

PubMed Central

Saha, Sudipto; Dazard, Jean-Eudes; Xu, Hua; Ewing, Rob M.

2013-01-01

Large-scale protein–protein interaction data sets have been generated for several species including yeast and human and have enabled the identification, quantification, and prediction of cellular molecular networks. Affinity purification-mass spectrometry (AP-MS) is the preeminent methodology for large-scale analysis of protein complexes, performed by immunopurifying a specific “bait” protein and its associated “prey” proteins. The analysis and interpretation of AP-MS data sets is, however, not straightforward. In addition, although yeast AP-MS data sets are relatively comprehensive, current human AP-MS data sets only sparsely cover the human interactome. Here we develop a framework for analysis of AP-MS data sets that addresses the issues of noise, missing data, and sparsity of coverage in the context of a current, real world human AP-MS data set. Our goal is to extend and increase the density of the known human interactome by integrating bait–prey and cocomplexed preys (prey–prey associations) into networks. Our framework incorporates a score for each identified protein, as well as elements of signal processing to improve the confidence of identified protein–protein interactions. We identify many protein networks enriched in known biological processes and functions. In addition, we show that integrated bait–prey and prey–prey interactions can be used to refine network topology and extend known protein networks. PMID:22845868

Inferring gene and protein interactions using PubMed citations and consensus Bayesian networks.

PubMed

Deeter, Anthony; Dalman, Mark; Haddad, Joseph; Duan, Zhong-Hui

2017-01-01

The PubMed database offers an extensive set of publication data that can be useful, yet inherently complex to use without automated computational techniques. Data repositories such as the Genomic Data Commons (GDC) and the Gene Expression Omnibus (GEO) offer experimental data storage and retrieval as well as curated gene expression profiles. Genetic interaction databases, including Reactome and Ingenuity Pathway Analysis, offer pathway and experiment data analysis using data curated from these publications and data repositories. We have created a method to generate and analyze consensus networks, inferring potential gene interactions, using large numbers of Bayesian networks generated by data mining publications in the PubMed database. Through the concept of network resolution, these consensus networks can be tailored to represent possible genetic interactions. We designed a set of experiments to confirm that our method is stable across variation in both sample and topological input sizes. Using gene product interactions from the KEGG pathway database and data mining PubMed publication abstracts, we verify that regardless of the network resolution or the inferred consensus network, our method is capable of inferring meaningful gene interactions through consensus Bayesian network generation with multiple, randomized topological orderings. Our method can not only confirm the existence of currently accepted interactions, but has the potential to hypothesize new ones as well. We show our method confirms the existence of known gene interactions such as JAK-STAT-PI3K-AKT-mTOR, infers novel gene interactions such as RAS- Bcl-2 and RAS-AKT, and found significant pathway-pathway interactions between the JAK-STAT signaling and Cardiac Muscle Contraction KEGG pathways.

Cluster Approach to Network Interaction in Pedagogical University

ERIC Educational Resources Information Center

Chekaleva, Nadezhda V.; Makarova, Natalia S.; Drobotenko, Yulia B.

2016-01-01

The study presented in the article is devoted to the analysis of theory and practice of network interaction within the framework of education clusters. Education clusters are considered to be a novel form of network interaction in pedagogical education in Russia. The aim of the article is to show the advantages and disadvantages of the cluster…

Identification of Modules in Protein-Protein Interaction Networks

NASA Astrophysics Data System (ADS)

Erten, Sinan; Koyutürk, Mehmet

In biological systems, most processes are carried out through orchestration of multiple interacting molecules. These interactions are often abstracted using network models. A key feature of cellular networks is their modularity, which contributes significantly to the robustness, as well as adaptability of biological systems. Therefore, modularization of cellular networks is likely to be useful in obtaining insights into the working principles of cellular systems, as well as building tractable models of cellular organization and dynamics. A common, high-throughput source of data on molecular interactions is in the form of physical interactions between proteins, which are organized into protein-protein interaction (PPI) networks. This chapter provides an overview on identification and analysis of functional modules in PPI networks, which has been an active area of research in the last decade.

Introduction to Social Network Analysis

NASA Astrophysics Data System (ADS)

Zaphiris, Panayiotis; Ang, Chee Siang

Social Network analysis focuses on patterns of relations between and among people, organizations, states, etc. It aims to describe networks of relations as fully as possible, identify prominent patterns in such networks, trace the flow of information through them, and discover what effects these relations and networks have on people and organizations. Social network analysis offers a very promising potential for analyzing human-human interactions in online communities (discussion boards, newsgroups, virtual organizations). This Tutorial provides an overview of this analytic technique and demonstrates how it can be used in Human Computer Interaction (HCI) research and practice, focusing especially on Computer Mediated Communication (CMC). This topic acquires particular importance these days, with the increasing popularity of social networking websites (e.g., youtube, myspace, MMORPGs etc.) and the research interest in studying them.

Integrative Analysis of Transcription Factor Combinatorial Interactions Using a Bayesian Tensor Factorization Approach

PubMed Central

Ye, Yusen; Gao, Lin; Zhang, Shihua

2017-01-01

Transcription factors play a key role in transcriptional regulation of genes and determination of cellular identity through combinatorial interactions. However, current studies about combinatorial regulation is deficient due to lack of experimental data in the same cellular environment and extensive existence of data noise. Here, we adopt a Bayesian CANDECOMP/PARAFAC (CP) factorization approach (BCPF) to integrate multiple datasets in a network paradigm for determining precise TF interaction landscapes. In our first application, we apply BCPF to integrate three networks built based on diverse datasets of multiple cell lines from ENCODE respectively to predict a global and precise TF interaction network. This network gives 38 novel TF interactions with distinct biological functions. In our second application, we apply BCPF to seven types of cell type TF regulatory networks and predict seven cell lineage TF interaction networks, respectively. By further exploring the dynamics and modularity of them, we find cell lineage-specific hub TFs participate in cell type or lineage-specific regulation by interacting with non-specific TFs. Furthermore, we illustrate the biological function of hub TFs by taking those of cancer lineage and blood lineage as examples. Taken together, our integrative analysis can reveal more precise and extensive description about human TF combinatorial interactions. PMID:29033978

Integrative Analysis of Transcription Factor Combinatorial Interactions Using a Bayesian Tensor Factorization Approach.

PubMed

Ye, Yusen; Gao, Lin; Zhang, Shihua

2017-01-01

Transcription factors play a key role in transcriptional regulation of genes and determination of cellular identity through combinatorial interactions. However, current studies about combinatorial regulation is deficient due to lack of experimental data in the same cellular environment and extensive existence of data noise. Here, we adopt a Bayesian CANDECOMP/PARAFAC (CP) factorization approach (BCPF) to integrate multiple datasets in a network paradigm for determining precise TF interaction landscapes. In our first application, we apply BCPF to integrate three networks built based on diverse datasets of multiple cell lines from ENCODE respectively to predict a global and precise TF interaction network. This network gives 38 novel TF interactions with distinct biological functions. In our second application, we apply BCPF to seven types of cell type TF regulatory networks and predict seven cell lineage TF interaction networks, respectively. By further exploring the dynamics and modularity of them, we find cell lineage-specific hub TFs participate in cell type or lineage-specific regulation by interacting with non-specific TFs. Furthermore, we illustrate the biological function of hub TFs by taking those of cancer lineage and blood lineage as examples. Taken together, our integrative analysis can reveal more precise and extensive description about human TF combinatorial interactions.

Network Analysis Reveals a Common Host-Pathogen Interaction Pattern in Arabidopsis Immune Responses.

PubMed

Li, Hong; Zhou, Yuan; Zhang, Ziding

2017-01-01

Many plant pathogens secrete virulence effectors into host cells to target important proteins in host cellular network. However, the dynamic interactions between effectors and host cellular network have not been fully understood. Here, an integrative network analysis was conducted by combining Arabidopsis thaliana protein-protein interaction network, known targets of Pseudomonas syringae and Hyaloperonospora arabidopsidis effectors, and gene expression profiles in the immune response. In particular, we focused on the characteristic network topology of the effector targets and differentially expressed genes (DEGs). We found that effectors tended to manipulate key network positions with higher betweenness centrality. The effector targets, especially those that are common targets of an individual effector, tended to be clustered together in the network. Moreover, the distances between the effector targets and DEGs increased over time during infection. In line with this observation, pathogen-susceptible mutants tended to have more DEGs surrounding the effector targets compared with resistant mutants. Our results suggest a common plant-pathogen interaction pattern at the cellular network level, where pathogens employ potent local impact mode to interfere with key positions in the host network, and plant organizes an in-depth defense by sequentially activating genes distal to the effector targets.

Ego Network Analysis of Upper Division Physics Student Survey

NASA Astrophysics Data System (ADS)

Brewe, Eric

2017-01-01

We present the analysis of student networks derived from a survey of upper division physics students. Ego networks focus on the connections that center on one person (the ego). The ego networks in this talk come from a survey that is part of an overall project focused on understanding student retention and persistence. The theory underlying this work is that social and academic integration are essential components to supporting students continued enrollment and ultimately graduation. This work uses network analysis as a way to investigate the role of social and academic interactions in retention and persistence decisions. We focus on student interactions with peers, on mentoring interactions with physics department faculty, and on engagement in physics groups and how they influence persistence. Our results, which are preliminary, will help frame the ongoing research project and identify ways in which departments can support students. This work supported by NSF grant #PHY 1344247.

Computational Analysis of Residue Interaction Networks and Coevolutionary Relationships in the Hsp70 Chaperones: A Community-Hopping Model of Allosteric Regulation and Communication

PubMed Central

Stetz, Gabrielle; Verkhivker, Gennady M.

2017-01-01

Allosteric interactions in the Hsp70 proteins are linked with their regulatory mechanisms and cellular functions. Despite significant progress in structural and functional characterization of the Hsp70 proteins fundamental questions concerning modularity of the allosteric interaction networks and hierarchy of signaling pathways in the Hsp70 chaperones remained largely unexplored and poorly understood. In this work, we proposed an integrated computational strategy that combined atomistic and coarse-grained simulations with coevolutionary analysis and network modeling of the residue interactions. A novel aspect of this work is the incorporation of dynamic residue correlations and coevolutionary residue dependencies in the construction of allosteric interaction networks and signaling pathways. We found that functional sites involved in allosteric regulation of Hsp70 may be characterized by structural stability, proximity to global hinge centers and local structural environment that is enriched by highly coevolving flexible residues. These specific characteristics may be necessary for regulation of allosteric structural transitions and could distinguish regulatory sites from nonfunctional conserved residues. The observed confluence of dynamics correlations and coevolutionary residue couplings with global networking features may determine modular organization of allosteric interactions and dictate localization of key mediating sites. Community analysis of the residue interaction networks revealed that concerted rearrangements of local interacting modules at the inter-domain interface may be responsible for global structural changes and a population shift in the DnaK chaperone. The inter-domain communities in the Hsp70 structures harbor the majority of regulatory residues involved in allosteric signaling, suggesting that these sites could be integral to the network organization and coordination of structural changes. Using a network-based formalism of allostery, we introduced a community-hopping model of allosteric communication. Atomistic reconstruction of signaling pathways in the DnaK structures captured a direction-specific mechanism and molecular details of signal transmission that are fully consistent with the mutagenesis experiments. The results of our study reconciled structural and functional experiments from a network-centric perspective by showing that global properties of the residue interaction networks and coevolutionary signatures may be linked with specificity and diversity of allosteric regulation mechanisms. PMID:28095400

Computational Analysis of Residue Interaction Networks and Coevolutionary Relationships in the Hsp70 Chaperones: A Community-Hopping Model of Allosteric Regulation and Communication.

PubMed

Stetz, Gabrielle; Verkhivker, Gennady M

2017-01-01

Allosteric interactions in the Hsp70 proteins are linked with their regulatory mechanisms and cellular functions. Despite significant progress in structural and functional characterization of the Hsp70 proteins fundamental questions concerning modularity of the allosteric interaction networks and hierarchy of signaling pathways in the Hsp70 chaperones remained largely unexplored and poorly understood. In this work, we proposed an integrated computational strategy that combined atomistic and coarse-grained simulations with coevolutionary analysis and network modeling of the residue interactions. A novel aspect of this work is the incorporation of dynamic residue correlations and coevolutionary residue dependencies in the construction of allosteric interaction networks and signaling pathways. We found that functional sites involved in allosteric regulation of Hsp70 may be characterized by structural stability, proximity to global hinge centers and local structural environment that is enriched by highly coevolving flexible residues. These specific characteristics may be necessary for regulation of allosteric structural transitions and could distinguish regulatory sites from nonfunctional conserved residues. The observed confluence of dynamics correlations and coevolutionary residue couplings with global networking features may determine modular organization of allosteric interactions and dictate localization of key mediating sites. Community analysis of the residue interaction networks revealed that concerted rearrangements of local interacting modules at the inter-domain interface may be responsible for global structural changes and a population shift in the DnaK chaperone. The inter-domain communities in the Hsp70 structures harbor the majority of regulatory residues involved in allosteric signaling, suggesting that these sites could be integral to the network organization and coordination of structural changes. Using a network-based formalism of allostery, we introduced a community-hopping model of allosteric communication. Atomistic reconstruction of signaling pathways in the DnaK structures captured a direction-specific mechanism and molecular details of signal transmission that are fully consistent with the mutagenesis experiments. The results of our study reconciled structural and functional experiments from a network-centric perspective by showing that global properties of the residue interaction networks and coevolutionary signatures may be linked with specificity and diversity of allosteric regulation mechanisms.

Latent Factors in Student-Teacher Interaction Factor Analysis

ERIC Educational Resources Information Center

Le, Thu; Bolt, Daniel; Camburn, Eric; Goff, Peter; Rohe, Karl

2017-01-01

Classroom interactions between students and teachers form a two-way or dyadic network. Measurements such as days absent, test scores, student ratings, or student grades can indicate the "quality" of the interaction. Together with the underlying bipartite graph, these values create a valued student-teacher dyadic interaction network. To…

Social Network Extraction and Analysis Based on Multimodal Dyadic Interaction

PubMed Central

Escalera, Sergio; Baró, Xavier; Vitrià, Jordi; Radeva, Petia; Raducanu, Bogdan

2012-01-01

Social interactions are a very important component in people’s lives. Social network analysis has become a common technique used to model and quantify the properties of social interactions. In this paper, we propose an integrated framework to explore the characteristics of a social network extracted from multimodal dyadic interactions. For our study, we used a set of videos belonging to New York Times’ Blogging Heads opinion blog. The Social Network is represented as an oriented graph, whose directed links are determined by the Influence Model. The links’ weights are a measure of the “influence” a person has over the other. The states of the Influence Model encode automatically extracted audio/visual features from our videos using state-of-the art algorithms. Our results are reported in terms of accuracy of audio/visual data fusion for speaker segmentation and centrality measures used to characterize the extracted social network. PMID:22438733

Protein interaction networks from literature mining

NASA Astrophysics Data System (ADS)

Ihara, Sigeo

2005-03-01

The ability to accurately predict and understand physiological changes in the biological network system in response to disease or drug therapeutics is of crucial importance in life science. The extensive amount of gene expression data generated from even a single microarray experiment often proves difficult to fully interpret and comprehend the biological significance. An increasing knowledge of protein interactions stored in the PubMed database, as well as the advancement of natural language processing, however, makes it possible to construct protein interaction networks from the gene expression information that are essential for understanding the biological meaning. From the in house literature mining system we have developed, the protein interaction network for humans was constructed. By analysis based on the graph-theoretical characterization of the total interaction network in literature, we found that the network is scale-free and semantic long-ranged interactions (i.e. inhibit, induce) between proteins dominate in the total interaction network, reducing the degree exponent. Interaction networks generated based on scientific text in which the interaction event is ambiguously described result in disconnected networks. In contrast interaction networks based on text in which the interaction events are clearly stated result in strongly connected networks. The results of protein-protein interaction networks obtained in real applications from microarray experiments are discussed: For example, comparisons of the gene expression data indicative of either a good or a poor prognosis for acute lymphoblastic leukemia with MLL rearrangements, using our system, showed newly discovered signaling cross-talk.

Temporal changes in the structure of a plant-frugivore network are influenced by bird migration and fruit availability

PubMed Central

Andresen, Ellen; Díaz-Castelazo, Cecilia

2016-01-01

Background. Ecological communities are dynamic collections whose composition and structure change over time, making up complex interspecific interaction networks. Mutualistic plant–animal networks can be approached through complex network analysis; these networks are characterized by a nested structure consisting of a core of generalist species, which endows the network with stability and robustness against disturbance. Those mutualistic network structures can vary as a consequence of seasonal fluctuations and food availability, as well as the arrival of new species into the system that might disorder the mutualistic network structure (e.g., a decrease in nested pattern). However, there is no assessment on how the arrival of migratory species into seasonal tropical systems can modify such patterns. Emergent and fine structural temporal patterns are adressed here for the first time for plant-frugivorous bird networks in a highly seasonal tropical environment. Methods. In a plant-frugivorous bird community, we analyzed the temporal turnover of bird species comprising the network core and periphery of ten temporal interaction networks resulting from different bird migration periods. Additionally, we evaluated how fruit abundance and richness, as well as the arrival of migratory birds into the system, explained the temporal changes in network parameters such as network size, connectance, nestedness, specialization, interaction strength asymmetry and niche overlap. The analysis included data from 10 quantitative plant-frugivorous bird networks registered from November 2013 to November 2014. Results. We registered a total of 319 interactions between 42 plant species and 44 frugivorous bird species; only ten bird species were part of the network core. We witnessed a noteworthy turnover of the species comprising the network periphery during migration periods, as opposed to the network core, which did not show significant temporal changes in species composition. Our results revealed that migration and fruit richness explain the temporal variations in network size, connectance, nestedness and interaction strength asymmetry. On the other hand, fruit abundance only explained connectance and nestedness. Discussion. By means of a fine-resolution temporal analysis, we evidenced for the first time how temporal changes in the interaction network structure respond to the arrival of migratory species into the system and to fruit availability. Additionally, few migratory bird species are important links for structuring networks, while most of them were peripheral species. We showed the relevance of studying bird–plant interactions at fine temporal scales, considering changing scenarios of species composition with a quantitative network approach. PMID:27330852

CollaborationViz: Interactive Visual Exploration of Biomedical Research Collaboration Networks

PubMed Central

Bian, Jiang; Xie, Mengjun; Hudson, Teresa J.; Eswaran, Hari; Brochhausen, Mathias; Hanna, Josh; Hogan, William R.

2014-01-01

Social network analysis (SNA) helps us understand patterns of interaction between social entities. A number of SNA studies have shed light on the characteristics of research collaboration networks (RCNs). Especially, in the Clinical Translational Science Award (CTSA) community, SNA provides us a set of effective tools to quantitatively assess research collaborations and the impact of CTSA. However, descriptive network statistics are difficult for non-experts to understand. In this article, we present our experiences of building meaningful network visualizations to facilitate a series of visual analysis tasks. The basis of our design is multidimensional, visual aggregation of network dynamics. The resulting visualizations can help uncover hidden structures in the networks, elicit new observations of the network dynamics, compare different investigators and investigator groups, determine critical factors to the network evolution, and help direct further analyses. We applied our visualization techniques to explore the biomedical RCNs at the University of Arkansas for Medical Sciences – a CTSA institution. And, we created CollaborationViz, an open-source visual analytical tool to help network researchers and administration apprehend the network dynamics of research collaborations through interactive visualization. PMID:25405477

Building a glaucoma interaction network using a text mining approach.

PubMed

Soliman, Maha; Nasraoui, Olfa; Cooper, Nigel G F

2016-01-01

The volume of biomedical literature and its underlying knowledge base is rapidly expanding, making it beyond the ability of a single human being to read through all the literature. Several automated methods have been developed to help make sense of this dilemma. The present study reports on the results of a text mining approach to extract gene interactions from the data warehouse of published experimental results which are then used to benchmark an interaction network associated with glaucoma. To the best of our knowledge, there is, as yet, no glaucoma interaction network derived solely from text mining approaches. The presence of such a network could provide a useful summative knowledge base to complement other forms of clinical information related to this disease. A glaucoma corpus was constructed from PubMed Central and a text mining approach was applied to extract genes and their relations from this corpus. The extracted relations between genes were checked using reference interaction databases and classified generally as known or new relations. The extracted genes and relations were then used to construct a glaucoma interaction network. Analysis of the resulting network indicated that it bears the characteristics of a small world interaction network. Our analysis showed the presence of seven glaucoma linked genes that defined the network modularity. A web-based system for browsing and visualizing the extracted glaucoma related interaction networks is made available at http://neurogene.spd.louisville.edu/GlaucomaINViewer/Form1.aspx. This study has reported the first version of a glaucoma interaction network using a text mining approach. The power of such an approach is in its ability to cover a wide range of glaucoma related studies published over many years. Hence, a bigger picture of the disease can be established. To the best of our knowledge, this is the first glaucoma interaction network to summarize the known literature. The major findings were a set of relations that could not be found in existing interaction databases and that were found to be new, in addition to a smaller subnetwork consisting of interconnected clusters of seven glaucoma genes. Future improvements can be applied towards obtaining a better version of this network.

Inferring gene and protein interactions using PubMed citations and consensus Bayesian networks

PubMed Central

Dalman, Mark; Haddad, Joseph; Duan, Zhong-Hui

2017-01-01

The PubMed database offers an extensive set of publication data that can be useful, yet inherently complex to use without automated computational techniques. Data repositories such as the Genomic Data Commons (GDC) and the Gene Expression Omnibus (GEO) offer experimental data storage and retrieval as well as curated gene expression profiles. Genetic interaction databases, including Reactome and Ingenuity Pathway Analysis, offer pathway and experiment data analysis using data curated from these publications and data repositories. We have created a method to generate and analyze consensus networks, inferring potential gene interactions, using large numbers of Bayesian networks generated by data mining publications in the PubMed database. Through the concept of network resolution, these consensus networks can be tailored to represent possible genetic interactions. We designed a set of experiments to confirm that our method is stable across variation in both sample and topological input sizes. Using gene product interactions from the KEGG pathway database and data mining PubMed publication abstracts, we verify that regardless of the network resolution or the inferred consensus network, our method is capable of inferring meaningful gene interactions through consensus Bayesian network generation with multiple, randomized topological orderings. Our method can not only confirm the existence of currently accepted interactions, but has the potential to hypothesize new ones as well. We show our method confirms the existence of known gene interactions such as JAK-STAT-PI3K-AKT-mTOR, infers novel gene interactions such as RAS- Bcl-2 and RAS-AKT, and found significant pathway-pathway interactions between the JAK-STAT signaling and Cardiac Muscle Contraction KEGG pathways. PMID:29049295

Applications of Social Network Analysis

NASA Astrophysics Data System (ADS)

Thilagam, P. Santhi

A social network [2] is a description of the social structure between actors, mostly persons, groups or organizations. It indicates the ways in which they are connected with each other by some relationship such as friendship, kinship, finance exchange etc. In a nutshell, when the person uses already known/unknown people to create new contacts, it forms social networking. The social network is not a new concept rather it can be formed when similar people interact with each other directly or indirectly to perform particular task. Examples of social networks include a friendship networks, collaboration networks, co-authorship networks, and co-employees networks which depict the direct interaction among the people. There are also other forms of social networks, such as entertainment networks, business Networks, citation networks, and hyperlink networks, in which interaction among the people is indirect. Generally, social networks operate on many levels, from families up to the level of nations and assists in improving interactive knowledge sharing, interoperability and collaboration.

DiffSLC: A graph centrality method to detect essential proteins of a protein-protein interaction network.

PubMed

Mistry, Divya; Wise, Roger P; Dickerson, Julie A

2017-01-01

Identification of central genes and proteins in biomolecular networks provides credible candidates for pathway analysis, functional analysis, and essentiality prediction. The DiffSLC centrality measure predicts central and essential genes and proteins using a protein-protein interaction network. Network centrality measures prioritize nodes and edges based on their importance to the network topology. These measures helped identify critical genes and proteins in biomolecular networks. The proposed centrality measure, DiffSLC, combines the number of interactions of a protein and the gene coexpression values of genes from which those proteins were translated, as a weighting factor to bias the identification of essential proteins in a protein interaction network. Potentially essential proteins with low node degree are promoted through eigenvector centrality. Thus, the gene coexpression values are used in conjunction with the eigenvector of the network's adjacency matrix and edge clustering coefficient to improve essentiality prediction. The outcome of this prediction is shown using three variations: (1) inclusion or exclusion of gene co-expression data, (2) impact of different coexpression measures, and (3) impact of different gene expression data sets. For a total of seven networks, DiffSLC is compared to other centrality measures using Saccharomyces cerevisiae protein interaction networks and gene expression data. Comparisons are also performed for the top ranked proteins against the known essential genes from the Saccharomyces Gene Deletion Project, which show that DiffSLC detects more essential proteins and has a higher area under the ROC curve than other compared methods. This makes DiffSLC a stronger alternative to other centrality methods for detecting essential genes using a protein-protein interaction network that obeys centrality-lethality principle. DiffSLC is implemented using the igraph package in R, and networkx package in Python. The python package can be obtained from git.io/diffslcpy. The R implementation and code to reproduce the analysis is available via git.io/diffslc.

Querying Large Biological Network Datasets

ERIC Educational Resources Information Center

Gulsoy, Gunhan

2013-01-01

New experimental methods has resulted in increasing amount of genetic interaction data to be generated every day. Biological networks are used to store genetic interaction data gathered. Increasing amount of data available requires fast large scale analysis methods. Therefore, we address the problem of querying large biological network datasets.…

Differential network analysis reveals the genome-wide landscape of estrogen receptor modulation in hormonal cancers

PubMed Central

Hsiao, Tzu-Hung; Chiu, Yu-Chiao; Hsu, Pei-Yin; Lu, Tzu-Pin; Lai, Liang-Chuan; Tsai, Mong-Hsun; Huang, Tim H.-M.; Chuang, Eric Y.; Chen, Yidong

2016-01-01

Several mutual information (MI)-based algorithms have been developed to identify dynamic gene-gene and function-function interactions governed by key modulators (genes, proteins, etc.). Due to intensive computation, however, these methods rely heavily on prior knowledge and are limited in genome-wide analysis. We present the modulated gene/gene set interaction (MAGIC) analysis to systematically identify genome-wide modulation of interaction networks. Based on a novel statistical test employing conjugate Fisher transformations of correlation coefficients, MAGIC features fast computation and adaption to variations of clinical cohorts. In simulated datasets MAGIC achieved greatly improved computation efficiency and overall superior performance than the MI-based method. We applied MAGIC to construct the estrogen receptor (ER) modulated gene and gene set (representing biological function) interaction networks in breast cancer. Several novel interaction hubs and functional interactions were discovered. ER+ dependent interaction between TGFβ and NFκB was further shown to be associated with patient survival. The findings were verified in independent datasets. Using MAGIC, we also assessed the essential roles of ER modulation in another hormonal cancer, ovarian cancer. Overall, MAGIC is a systematic framework for comprehensively identifying and constructing the modulated interaction networks in a whole-genome landscape. MATLAB implementation of MAGIC is available for academic uses at https://github.com/chiuyc/MAGIC. PMID:26972162

A Preliminary Examination of the Relationship Between Social Networking Interactions, Internet Use, and Thwarted Belongingness.

PubMed

Moberg, Fallon B; Anestis, Michael D

2015-01-01

Joiner's (2005) interpersonal-psychological theory of suicide hypothesizes that suicidal desire develops in response to the joint presence of thwarted belongingness and perceived burdensomeness. To consider the potential influence of online interactions and behaviors on these outcomes. To address this, we administered an online protocol assessing suicidal desire and online interactions in a sample of 305 undergraduates (83.6% female). We hypothesized negative interactions on social networking sites and a preference for online social interactions would be associated with thwarted belongingness. We also conducted an exploratory analysis examining the associations between Internet usage and perceived burdensomeness. Higher levels of negative interactions on social networking sites, but no other variables, significantly predicted thwarted belongingness. Our exploratory analysis showed that none of our predictors were associated with perceived burdensomeness after accounting for demographics, depression, and thwarted belongingness. Our findings indicate that a general tendency to have negative interactions on social networking sites could possibly impact suicidal desire and that these effects are significant above and beyond depression symptoms. Furthermore, no other aspect of problematic Internet use significantly predicted our outcomes in multivariate analyses, indicating that social networking in particular may have a robust effect on thwarted belongingness.

Extensive cross-talk and global regulators identified from an analysis of the integrated transcriptional and signaling network in Escherichia coli.

PubMed

Antiqueira, Lucas; Janga, Sarath Chandra; Costa, Luciano da Fontoura

2012-11-01

To understand the regulatory dynamics of transcription factors (TFs) and their interplay with other cellular components we have integrated transcriptional, protein-protein and the allosteric or equivalent interactions which mediate the physiological activity of TFs in Escherichia coli. To study this integrated network we computed a set of network measurements followed by principal component analysis (PCA), investigated the correlations between network structure and dynamics, and carried out a procedure for motif detection. In particular, we show that outliers identified in the integrated network based on their network properties correspond to previously characterized global transcriptional regulators. Furthermore, outliers are highly and widely expressed across conditions, thus supporting their global nature in controlling many genes in the cell. Motifs revealed that TFs not only interact physically with each other but also obtain feedback from signals delivered by signaling proteins supporting the extensive cross-talk between different types of networks. Our analysis can lead to the development of a general framework for detecting and understanding global regulatory factors in regulatory networks and reinforces the importance of integrating multiple types of interactions in underpinning the interrelationships between them.

A Multidimensional Analysis Tool for Visualizing Online Interactions

ERIC Educational Resources Information Center

Kim, Minjeong; Lee, Eunchul

2012-01-01

This study proposes and verifies the performance of an analysis tool for visualizing online interactions. A review of the most widely used methods for analyzing online interactions, including quantitative analysis, content analysis, and social network analysis methods, indicates these analysis methods have some limitations resulting from their…

Exploring Classroom Interaction with Dynamic Social Network Analysis

ERIC Educational Resources Information Center

Bokhove, Christian

2018-01-01

This article reports on an exploratory project in which technology and dynamic social network analysis (SNA) are used for modelling classroom interaction. SNA focuses on the links between social actors, draws on graphic imagery to reveal and display the patterning of those links, and develops mathematical and computational models to describe and…

Coexpression network based on natural variation in human gene expression reveals gene interactions and functions

PubMed Central

Nayak, Renuka R.; Kearns, Michael; Spielman, Richard S.; Cheung, Vivian G.

2009-01-01

Genes interact in networks to orchestrate cellular processes. Analysis of these networks provides insights into gene interactions and functions. Here, we took advantage of normal variation in human gene expression to infer gene networks, which we constructed using correlations in expression levels of more than 8.5 million gene pairs in immortalized B cells from three independent samples. The resulting networks allowed us to identify biological processes and gene functions. Among the biological pathways, we found processes such as translation and glycolysis that co-occur in the same subnetworks. We predicted the functions of poorly characterized genes, including CHCHD2 and TMEM111, and provided experimental evidence that TMEM111 is part of the endoplasmic reticulum-associated secretory pathway. We also found that IFIH1, a susceptibility gene of type 1 diabetes, interacts with YES1, which plays a role in glucose transport. Furthermore, genes that predispose to the same diseases are clustered nonrandomly in the coexpression network, suggesting that networks can provide candidate genes that influence disease susceptibility. Therefore, our analysis of gene coexpression networks offers information on the role of human genes in normal and disease processes. PMID:19797678

Using the clustered circular layout as an informative method for visualizing protein-protein interaction networks.

PubMed

Fung, David C Y; Wilkins, Marc R; Hart, David; Hong, Seok-Hee

2010-07-01

The force-directed layout is commonly used in computer-generated visualizations of protein-protein interaction networks. While it is good for providing a visual outline of the protein complexes and their interactions, it has two limitations when used as a visual analysis method. The first is poor reproducibility. Repeated running of the algorithm does not necessarily generate the same layout, therefore, demanding cognitive readaptation on the investigator's part. The second limitation is that it does not explicitly display complementary biological information, e.g. Gene Ontology, other than the protein names or gene symbols. Here, we present an alternative layout called the clustered circular layout. Using the human DNA replication protein-protein interaction network as a case study, we compared the two network layouts for their merits and limitations in supporting visual analysis.

Protein-protein interaction network of gene expression in the hydrocortisone-treated keloid.

PubMed

Chen, Rui; Zhang, Zhiliang; Xue, Zhujia; Wang, Lin; Fu, Mingang; Lu, Yi; Bai, Ling; Zhang, Ping; Fan, Zhihong

2015-01-01

In order to explore the molecular mechanism of hydrocortisone in keloid tissue, the gene expression profiles of keloid samples treated with hydrocortisone were subjected to bioinformatics analysis. Firstly, the gene expression profiles (GSE7890) of five samples of keloid treated with hydrocortisone and five untreated keloid samples were downloaded from the Gene Expression Omnibus (GEO) database. Secondly, data were preprocessed using packages in R language and differentially expressed genes (DEGs) were screened using a significance analysis of microarrays (SAM) protocol. Thirdly, the DEGs were subjected to gene ontology (GO) function and KEGG pathway enrichment analysis. Finally, the interactions of DEGs in samples of keloid treated with hydrocortisone were explored in a human protein-protein interaction (PPI) network, and sub-modules of the DEGs interaction network were analyzed using Cytoscape software. Based on the analysis, 572 DEGs in the hydrocortisone-treated samples were screened; most of these were involved in the signal transduction and cell cycle. Furthermore, three critical genes in the module, including COL1A1, NID1, and PRELP, were screened in the PPI network analysis. These findings enhance understanding of the pathogenesis of the keloid and provide references for keloid therapy. © 2015 The International Society of Dermatology.

A dedicated network for social interaction processing in the primate brain.

PubMed

Sliwa, J; Freiwald, W A

2017-05-19

Primate cognition requires interaction processing. Interactions can reveal otherwise hidden properties of intentional agents, such as thoughts and feelings, and of inanimate objects, such as mass and material. Where and how interaction analyses are implemented in the brain is unknown. Using whole-brain functional magnetic resonance imaging in macaque monkeys, we discovered a network centered in the medial and ventrolateral prefrontal cortex that is exclusively engaged in social interaction analysis. Exclusivity of specialization was found for no other function anywhere in the brain. Two additional networks, a parieto-premotor and a temporal one, exhibited both social and physical interaction preference, which, in the temporal lobe, mapped onto a fine-grain pattern of object, body, and face selectivity. Extent and location of a dedicated system for social interaction analysis suggest that this function is an evolutionary forerunner of human mind-reading capabilities. Copyright © 2017, American Association for the Advancement of Science.

MONGKIE: an integrated tool for network analysis and visualization for multi-omics data.

PubMed

Jang, Yeongjun; Yu, Namhee; Seo, Jihae; Kim, Sun; Lee, Sanghyuk

2016-03-18

Network-based integrative analysis is a powerful technique for extracting biological insights from multilayered omics data such as somatic mutations, copy number variations, and gene expression data. However, integrated analysis of multi-omics data is quite complicated and can hardly be done in an automated way. Thus, a powerful interactive visual mining tool supporting diverse analysis algorithms for identification of driver genes and regulatory modules is much needed. Here, we present a software platform that integrates network visualization with omics data analysis tools seamlessly. The visualization unit supports various options for displaying multi-omics data as well as unique network models for describing sophisticated biological networks such as complex biomolecular reactions. In addition, we implemented diverse in-house algorithms for network analysis including network clustering and over-representation analysis. Novel functions include facile definition and optimized visualization of subgroups, comparison of a series of data sets in an identical network by data-to-visual mapping and subsequent overlaying function, and management of custom interaction networks. Utility of MONGKIE for network-based visual data mining of multi-omics data was demonstrated by analysis of the TCGA glioblastoma data. MONGKIE was developed in Java based on the NetBeans plugin architecture, thus being OS-independent with intrinsic support of module extension by third-party developers. We believe that MONGKIE would be a valuable addition to network analysis software by supporting many unique features and visualization options, especially for analysing multi-omics data sets in cancer and other diseases. .

Structural diversity effects of multilayer networks on the threshold of interacting epidemics

NASA Astrophysics Data System (ADS)

Wang, Weihong; Chen, MingMing; Min, Yong; Jin, Xiaogang

2016-02-01

Foodborne diseases always spread through multiple vectors (e.g. fresh vegetables and fruits) and reveal that multilayer network could spread fatal pathogen with complex interactions. In this paper, first, we use a "top-down analysis framework that depends on only two distributions to describe a random multilayer network with any number of layers. These two distributions are the overlaid degree distribution and the edge-type distribution of the multilayer network. Second, based on the two distributions, we adopt three indicators of multilayer network diversity to measure the correlation between network layers, including network richness, likeness, and evenness. The network richness is the number of layers forming the multilayer network. The network likeness is the degree of different layers sharing the same edge. The network evenness is the variance of the number of edges in every layer. Third, based on a simple epidemic model, we analyze the influence of network diversity on the threshold of interacting epidemics with the coexistence of collaboration and competition. Our work extends the "top-down" analysis framework to deal with the more complex epidemic situation and more diversity indicators and quantifies the trade-off between thresholds of inter-layer collaboration and intra-layer transmission.

Investigating student communities with network analysis of interactions in a physics learning center

NASA Astrophysics Data System (ADS)

Brewe, Eric; Kramer, Laird; Sawtelle, Vashti

2012-06-01

Developing a sense of community among students is one of the three pillars of an overall reform effort to increase participation in physics, and the sciences more broadly, at Florida International University. The emergence of a research and learning community, embedded within a course reform effort, has contributed to increased recruitment and retention of physics majors. We utilize social network analysis to quantify interactions in Florida International University’s Physics Learning Center (PLC) that support the development of academic and social integration. The tools of social network analysis allow us to visualize and quantify student interactions and characterize the roles of students within a social network. After providing a brief introduction to social network analysis, we use sequential multiple regression modeling to evaluate factors that contribute to participation in the learning community. Results of the sequential multiple regression indicate that the PLC learning community is an equitable environment as we find that gender and ethnicity are not significant predictors of participation in the PLC. We find that providing students space for collaboration provides a vital element in the formation of a supportive learning community.

Mixed-method Exploration of Social Network Links to Participation

PubMed Central

Kreider, Consuelo M.; Bendixen, Roxanna M.; Mann, William C.; Young, Mary Ellen; McCarty, Christopher

2015-01-01

The people who regularly interact with an adolescent form that youth's social network, which may impact participation. We investigated the relationship of social networks to participation using personal network analysis and individual interviews. The sample included 36 youth, age 11 – 16 years. Nineteen had diagnoses of learning disability, attention disorder, or high-functioning autism and 17 were typically developing. Network analysis yielded 10 network variables, of which 8 measured network composition and 2 measured network structure, with significant links to at least one measure of participation using the Children's Assessment of Participation and Enjoyment (CAPE). Interviews from youth in the clinical group yielded description of strategies used to negotiate social interactions, as well as processes and reasoning used to remain engaged within social networks. Findings contribute to understanding the ways social networks are linked to youth participation and suggest the potential of social network factors for predicting rehabilitation outcomes. PMID:26594737

Clustering drug-drug interaction networks with energy model layouts: community analysis and drug repurposing.

PubMed

Udrescu, Lucreţia; Sbârcea, Laura; Topîrceanu, Alexandru; Iovanovici, Alexandru; Kurunczi, Ludovic; Bogdan, Paul; Udrescu, Mihai

2016-09-07

Analyzing drug-drug interactions may unravel previously unknown drug action patterns, leading to the development of new drug discovery tools. We present a new approach to analyzing drug-drug interaction networks, based on clustering and topological community detection techniques that are specific to complex network science. Our methodology uncovers functional drug categories along with the intricate relationships between them. Using modularity-based and energy-model layout community detection algorithms, we link the network clusters to 9 relevant pharmacological properties. Out of the 1141 drugs from the DrugBank 4.1 database, our extensive literature survey and cross-checking with other databases such as Drugs.com, RxList, and DrugBank 4.3 confirm the predicted properties for 85% of the drugs. As such, we argue that network analysis offers a high-level grasp on a wide area of pharmacological aspects, indicating possible unaccounted interactions and missing pharmacological properties that can lead to drug repositioning for the 15% drugs which seem to be inconsistent with the predicted property. Also, by using network centralities, we can rank drugs according to their interaction potential for both simple and complex multi-pathology therapies. Moreover, our clustering approach can be extended for applications such as analyzing drug-target interactions or phenotyping patients in personalized medicine applications.

Clustering drug-drug interaction networks with energy model layouts: community analysis and drug repurposing

PubMed Central

Udrescu, Lucreţia; Sbârcea, Laura; Topîrceanu, Alexandru; Iovanovici, Alexandru; Kurunczi, Ludovic; Bogdan, Paul; Udrescu, Mihai

2016-01-01

Analyzing drug-drug interactions may unravel previously unknown drug action patterns, leading to the development of new drug discovery tools. We present a new approach to analyzing drug-drug interaction networks, based on clustering and topological community detection techniques that are specific to complex network science. Our methodology uncovers functional drug categories along with the intricate relationships between them. Using modularity-based and energy-model layout community detection algorithms, we link the network clusters to 9 relevant pharmacological properties. Out of the 1141 drugs from the DrugBank 4.1 database, our extensive literature survey and cross-checking with other databases such as Drugs.com, RxList, and DrugBank 4.3 confirm the predicted properties for 85% of the drugs. As such, we argue that network analysis offers a high-level grasp on a wide area of pharmacological aspects, indicating possible unaccounted interactions and missing pharmacological properties that can lead to drug repositioning for the 15% drugs which seem to be inconsistent with the predicted property. Also, by using network centralities, we can rank drugs according to their interaction potential for both simple and complex multi-pathology therapies. Moreover, our clustering approach can be extended for applications such as analyzing drug-target interactions or phenotyping patients in personalized medicine applications. PMID:27599720

Social network analysis of character interaction in the Stargate and Star Trek television series

NASA Astrophysics Data System (ADS)

Tan, Melody Shi Ai; Ujum, Ephrance Abu; Ratnavelu, Kuru

This paper undertakes a social network analysis of two science fiction television series, Stargate and Star Trek. Television series convey stories in the form of character interaction, which can be represented as “character networks”. We connect each pair of characters that exchanged spoken dialogue in any given scene demarcated in the television series transcripts. These networks are then used to characterize the overall structure and topology of each series. We find that the character networks of both series have similar structure and topology to that found in previous work on mythological and fictional networks. The character networks exhibit the small-world effects but found no significant support for power-law. Since the progression of an episode depends to a large extent on the interaction between each of its characters, the underlying network structure tells us something about the complexity of that episode’s storyline. We assessed the complexity using techniques from spectral graph theory. We found that the episode networks are structured either as (1) closed networks, (2) those containing bottlenecks that connect otherwise disconnected clusters or (3) a mixture of both.

Speech networks at rest and in action: interactions between functional brain networks controlling speech production.

PubMed

Simonyan, Kristina; Fuertinger, Stefan

2015-04-01

Speech production is one of the most complex human behaviors. Although brain activation during speaking has been well investigated, our understanding of interactions between the brain regions and neural networks remains scarce. We combined seed-based interregional correlation analysis with graph theoretical analysis of functional MRI data during the resting state and sentence production in healthy subjects to investigate the interface and topology of functional networks originating from the key brain regions controlling speech, i.e., the laryngeal/orofacial motor cortex, inferior frontal and superior temporal gyri, supplementary motor area, cingulate cortex, putamen, and thalamus. During both resting and speaking, the interactions between these networks were bilaterally distributed and centered on the sensorimotor brain regions. However, speech production preferentially recruited the inferior parietal lobule (IPL) and cerebellum into the large-scale network, suggesting the importance of these regions in facilitation of the transition from the resting state to speaking. Furthermore, the cerebellum (lobule VI) was the most prominent region showing functional influences on speech-network integration and segregation. Although networks were bilaterally distributed, interregional connectivity during speaking was stronger in the left vs. right hemisphere, which may have underlined a more homogeneous overlap between the examined networks in the left hemisphere. Among these, the laryngeal motor cortex (LMC) established a core network that fully overlapped with all other speech-related networks, determining the extent of network interactions. Our data demonstrate complex interactions of large-scale brain networks controlling speech production and point to the critical role of the LMC, IPL, and cerebellum in the formation of speech production network. Copyright © 2015 the American Physiological Society.

Insight into bacterial virulence mechanisms against host immune response via the Yersinia pestis-human protein-protein interaction network.

PubMed

Yang, Huiying; Ke, Yuehua; Wang, Jian; Tan, Yafang; Myeni, Sebenzile K; Li, Dong; Shi, Qinghai; Yan, Yanfeng; Chen, Hui; Guo, Zhaobiao; Yuan, Yanzhi; Yang, Xiaoming; Yang, Ruifu; Du, Zongmin

2011-11-01

A Yersinia pestis-human protein interaction network is reported here to improve our understanding of its pathogenesis. Up to 204 interactions between 66 Y. pestis bait proteins and 109 human proteins were identified by yeast two-hybrid assay and then combined with 23 previously published interactions to construct a protein-protein interaction network. Topological analysis of the interaction network revealed that human proteins targeted by Y. pestis were significantly enriched in the proteins that are central in the human protein-protein interaction network. Analysis of this network showed that signaling pathways important for host immune responses were preferentially targeted by Y. pestis, including the pathways involved in focal adhesion, regulation of cytoskeleton, leukocyte transendoepithelial migration, and Toll-like receptor (TLR) and mitogen-activated protein kinase (MAPK) signaling. Cellular pathways targeted by Y. pestis are highly relevant to its pathogenesis. Interactions with host proteins involved in focal adhesion and cytoskeketon regulation pathways could account for resistance of Y. pestis to phagocytosis. Interference with TLR and MAPK signaling pathways by Y. pestis reflects common characteristics of pathogen-host interaction that bacterial pathogens have evolved to evade host innate immune response by interacting with proteins in those signaling pathways. Interestingly, a large portion of human proteins interacting with Y. pestis (16/109) also interacted with viral proteins (Epstein-Barr virus [EBV] and hepatitis C virus [HCV]), suggesting that viral and bacterial pathogens attack common cellular functions to facilitate infections. In addition, we identified vasodilator-stimulated phosphoprotein (VASP) as a novel interaction partner of YpkA and showed that YpkA could inhibit in vitro actin assembly mediated by VASP.

Interactions between Niche and Regime: An Analysis of Learning and Innovation Networks for Sustainable Agriculture across Europe

ERIC Educational Resources Information Center

Ingram, Julie; Maye, Damian; Kirwan, James; Curry, Nigel; Kubinakova, Katarina

2015-01-01

Purpose: This paper aims to reveal, and contribute to an understanding of, the processes that connect learning and innovation networks in sustainable agriculture to elements of the mainstream agricultural regime. Drawing on the innovations and transition literature, the paper frames the analysis around niche-regime interaction using the notion of…

Visualisation and graph-theoretic analysis of a large-scale protein structural interactome

PubMed Central

Bolser, Dan; Dafas, Panos; Harrington, Richard; Park, Jong; Schroeder, Michael

2003-01-01

Background Large-scale protein interaction maps provide a new, global perspective with which to analyse protein function. PSIMAP, the Protein Structural Interactome Map, is a database of all the structurally observed interactions between superfamilies of protein domains with known three-dimensional structure in the PDB. PSIMAP incorporates both functional and evolutionary information into a single network. Results We present a global analysis of PSIMAP using several distinct network measures relating to centrality, interactivity, fault-tolerance, and taxonomic diversity. We found the following results: Centrality: we show that the center and barycenter of PSIMAP do not coincide, and that the superfamilies forming the barycenter relate to very general functions, while those constituting the center relate to enzymatic activity. Interactivity: we identify the P-loop and immunoglobulin superfamilies as the most highly interactive. We successfully use connectivity and cluster index, which characterise the connectivity of a superfamily's neighbourhood, to discover superfamilies of complex I and II. This is particularly significant as the structure of complex I is not yet solved. Taxonomic diversity: we found that highly interactive superfamilies are in general taxonomically very diverse and are thus amongst the oldest. Fault-tolerance: we found that the network is very robust as for the majority of superfamilies removal from the network will not break up the network. Conclusions Overall, we can single out the P-loop containing nucleotide triphosphate hydrolases superfamily as it is the most highly connected and has the highest taxonomic diversity. In addition, this superfamily has the highest interaction rank, is the barycenter of the network (it has the shortest average path to every other superfamily in the network), and is an articulation vertex, whose removal will disconnect the network. More generally, we conclude that the graph-theoretic and taxonomic analysis of PSIMAP is an important step towards the understanding of protein function and could be an important tool for tracing the evolution of life at the molecular level. PMID:14531933

Social Network Analysis in E-Learning Environments: A Preliminary Systematic Review

ERIC Educational Resources Information Center

Cela, Karina L.; Sicilia, Miguel Ángel; Sánchez, Salvador

2015-01-01

E-learning occupies an increasingly prominent place in education. It provides the learner with a rich virtual network where he or she can exchange ideas and information and create synergies through interactions with other members of the network, whether fellow learners or teachers. Social network analysis (SNA) has proven extremely powerful at…

Decreased functional connectivity to posterior cingulate cortex in major depressive disorder.

PubMed

Yang, Rui; Gao, Chengge; Wu, Xiaoping; Yang, Junle; Li, Shengbin; Cheng, Hu

2016-09-30

The default mode network (DMN) and its interaction with other key networks such as the salience network and executive network are keys to understand psychiatric and neurological disorders including major depressive disorder (MDD). In this study, we combined independent component analysis and seed based connectivity analysis to study the posterior default mode network between 20 patients with MDD and 25 normal controls, as well as pre-treatment and post-treatment conditions of the patients. Both correlated and anti-correlated networks centered at the posterior cingulate cortex (PCC) were examined (PCC+ and PCC-). Our results showed aberrant functional connectivity of the PCC+ and PCC- networks between patients and normal controls. Specifically, normal controls exhibited significantly higher connectivity between the PCC and frontal/temporal regions for the PCC+ network and stronger connectivity strength between the PCC and the insula/middle frontal cortex for the PCC- network. The overall connectivity strength of the PCC+ and PCC- networks was also significantly lower in MDD. Because the PCC is a hub in the DMN that interacts with other networks, our result suggested a stronger interaction between the DMN and the salience network but a weak interaction between the DMN and the executive network in MDD. The treatment using sertraline did increase the functional connectivity strength, especially in the PCC+ network. Despite a large inter-subject variability in the overall connectivity strengths and change of the PCC network in response to the treatment, a high correlation between change of connectivity strength and the Hamilton depression score was observed for both the PCC+ and PCC- network. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Prediction and functional analysis of the sweet orange protein-protein interaction network.

PubMed

Ding, Yu-Duan; Chang, Ji-Wei; Guo, Jing; Chen, Dijun; Li, Sen; Xu, Qiang; Deng, Xiu-Xin; Cheng, Yun-Jiang; Chen, Ling-Ling

2014-08-05

Sweet orange (Citrus sinensis) is one of the most important fruits world-wide. Because it is a woody plant with a long growth cycle, genetic studies of sweet orange are lagging behind those of other species. In this analysis, we employed ortholog identification and domain combination methods to predict the protein-protein interaction (PPI) network for sweet orange. The K-nearest neighbors (KNN) classification method was used to verify and filter the network. The final predicted PPI network, CitrusNet, contained 8,195 proteins with 124,491 interactions. The quality of CitrusNet was evaluated using gene ontology (GO) and Mapman annotations, which confirmed the reliability of the network. In addition, we calculated the expression difference of interacting genes (EDI) in CitrusNet using RNA-seq data from four sweet orange tissues, and also analyzed the EDI distribution and variation in different sub-networks. Gene expression in CitrusNet has significant modular features. Target of rapamycin (TOR) protein served as the central node of the hormone-signaling sub-network. All evidence supported the idea that TOR can integrate various hormone signals and affect plant growth. CitrusNet provides valuable resources for the study of biological functions in sweet orange.

Understanding Classrooms through Social Network Analysis: A Primer for Social Network Analysis in Education Research

ERIC Educational Resources Information Center

Grunspan, Daniel Z.; Wiggins, Benjamin L.; Goodreau, Steven M.

2014-01-01

Social interactions between students are a major and underexplored part of undergraduate education. Understanding how learning relationships form in undergraduate classrooms, as well as the impacts these relationships have on learning outcomes, can inform educators in unique ways and improve educational reform. Social network analysis (SNA)…

Creative constraints: Brain activity and network dynamics underlying semantic interference during idea production.

PubMed

Beaty, Roger E; Christensen, Alexander P; Benedek, Mathias; Silvia, Paul J; Schacter, Daniel L

2017-03-01

Functional neuroimaging research has recently revealed brain network interactions during performance on creative thinking tasks-particularly among regions of the default and executive control networks-but the cognitive mechanisms related to these interactions remain poorly understood. Here we test the hypothesis that the executive control network can interact with the default network to inhibit salient conceptual knowledge (i.e., pre-potent responses) elicited from memory during creative idea production. Participants studied common noun-verb pairs and were given a cued-recall test with corrective feedback to strengthen the paired association in memory. They then completed a verb generation task that presented either a previously studied noun (high-constraint) or an unstudied noun (low-constraint), and were asked to "think creatively" while searching for a novel verb to relate to the presented noun. Latent Semantic Analysis of verbal responses showed decreased semantic distance values in the high-constraint (i.e., interference) condition, which corresponded to increased neural activity within regions of the default (posterior cingulate cortex and bilateral angular gyri), salience (right anterior insula), and executive control (left dorsolateral prefrontal cortex) networks. Independent component analysis of intrinsic functional connectivity networks extended this finding by revealing differential interactions among these large-scale networks across the task conditions. The results suggest that interactions between the default and executive control networks underlie response inhibition during constrained idea production, providing insight into specific neurocognitive mechanisms supporting creative cognition. Copyright © 2017 Elsevier Inc. All rights reserved.

Dynamical analysis of yeast protein interaction network during the sake brewing process.

PubMed

Mirzarezaee, Mitra; Sadeghi, Mehdi; Araabi, Babak N

2011-12-01

Proteins interact with each other for performing essential functions of an organism. They change partners to get involved in various processes at different times or locations. Studying variations of protein interactions within a specific process would help better understand the dynamic features of the protein interactions and their functions. We studied the protein interaction network of Saccharomyces cerevisiae (yeast) during the brewing of Japanese sake. In this process, yeast cells are exposed to several stresses. Analysis of protein interaction networks of yeast during this process helps to understand how protein interactions of yeast change during the sake brewing process. We used gene expression profiles of yeast cells for this purpose. Results of our experiments revealed some characteristics and behaviors of yeast hubs and non-hubs and their dynamical changes during the brewing process. We found that just a small portion of the proteins (12.8 to 21.6%) is responsible for the functional changes of the proteins in the sake brewing process. The changes in the number of edges and hubs of the yeast protein interaction networks increase in the first stages of the process and it then decreases at the final stages.

gRINN: a tool for calculation of residue interaction energies and protein energy network analysis of molecular dynamics simulations.

PubMed

Serçinoglu, Onur; Ozbek, Pemra

2018-05-25

Atomistic molecular dynamics (MD) simulations generate a wealth of information related to the dynamics of proteins. If properly analyzed, this information can lead to new insights regarding protein function and assist wet-lab experiments. Aiming to identify interactions between individual amino acid residues and the role played by each in the context of MD simulations, we present a stand-alone software called gRINN (get Residue Interaction eNergies and Networks). gRINN features graphical user interfaces (GUIs) and a command-line interface for generating and analyzing pairwise residue interaction energies and energy correlations from protein MD simulation trajectories. gRINN utilizes the features of NAMD or GROMACS MD simulation packages and automatizes the steps necessary to extract residue-residue interaction energies from user-supplied simulation trajectories, greatly simplifying the analysis for the end-user. A GUI, including an embedded molecular viewer, is provided for visualization of interaction energy time-series, distributions, an interaction energy matrix, interaction energy correlations and a residue correlation matrix. gRINN additionally offers construction and analysis of Protein Energy Networks, providing residue-based metrics such as degrees, betweenness-centralities, closeness centralities as well as shortest path analysis. gRINN is free and open to all users without login requirement at http://grinn.readthedocs.io.

BiNA: A Visual Analytics Tool for Biological Network Data

PubMed Central

Gerasch, Andreas; Faber, Daniel; Küntzer, Jan; Niermann, Peter; Kohlbacher, Oliver; Lenhof, Hans-Peter; Kaufmann, Michael

2014-01-01

Interactive visual analysis of biological high-throughput data in the context of the underlying networks is an essential task in modern biomedicine with applications ranging from metabolic engineering to personalized medicine. The complexity and heterogeneity of data sets require flexible software architectures for data analysis. Concise and easily readable graphical representation of data and interactive navigation of large data sets are essential in this context. We present BiNA - the Biological Network Analyzer - a flexible open-source software for analyzing and visualizing biological networks. Highly configurable visualization styles for regulatory and metabolic network data offer sophisticated drawings and intuitive navigation and exploration techniques using hierarchical graph concepts. The generic projection and analysis framework provides powerful functionalities for visual analyses of high-throughput omics data in the context of networks, in particular for the differential analysis and the analysis of time series data. A direct interface to an underlying data warehouse provides fast access to a wide range of semantically integrated biological network databases. A plugin system allows simple customization and integration of new analysis algorithms or visual representations. BiNA is available under the 3-clause BSD license at http://bina.unipax.info/. PMID:24551056

Ant-Plant Interaction in a Tropical Savanna: May the Network Structure Vary over Time and Influence on the Outcomes of Associations?

PubMed Central

Lange, Denise; Del-Claro, Kleber

2014-01-01

Plant-animal interactions occur in a community context of dynamic and complex ecological interactive networks. The understanding of who interacts with whom is a basic information, but the outcomes of interactions among associates are fundamental to draw valid conclusions about the functional structure of the network. Ecological networks studies in general gave little importance to know the true outcomes of interactions and how they may change over time. We evaluate the dynamic of an interaction network between ants and plants with extrafloral nectaries, by verifying the temporal variation in structure and outcomes of mutualism for the plant community (leaf herbivory). To reach this goal, we used two tools: bipartite network analysis and experimental manipulation. The networks exhibited the same general pattern as other mutualistic networks: nestedness, asymmetry and low specialization and this pattern was maintained over time, but with internal changes (species degree, connectance and ant abundance). These changes influenced the protection effectiveness of plants by ants, which varied over time. Our study shows that interaction networks between ants and plants are dynamic over time, and that these alterations affect the outcomes of mutualisms. In addition, our study proposes that the set of single systems that shape ecological networks can be manipulated for a greater understanding of the entire system. PMID:25141007

Mass Spectrometry Analysis of Spatial Protein Networks by Colocalization Analysis (COLA).

PubMed

Mardakheh, Faraz K

2017-01-01

A major challenge in systems biology is comprehensive mapping of protein interaction networks. Crucially, such interactions are often dynamic in nature, necessitating methods that can rapidly mine the interactome across varied conditions and treatments to reveal change in the interaction networks. Recently, we described a fast mass spectrometry-based method to reveal functional interactions in mammalian cells on a global scale, by revealing spatial colocalizations between proteins (COLA) (Mardakheh et al., Mol Biosyst 13:92-105, 2017). As protein localization and function are inherently linked, significant colocalization between two proteins is a strong indication for their functional interaction. COLA uses rapid complete subcellular fractionation, coupled with quantitative proteomics to generate a subcellular localization profile for each protein quantified by the mass spectrometer. Robust clustering is then applied to reveal significant similarities in protein localization profiles, indicative of colocalization.

Does the social capital in networks of “fish and fire” scientists and managers suggest learning?

Treesearch

A. Paige Fischer; Ken Vance-Borland; Kelly M. Burnett; Susan Hummel; Janean H. Creighton; Sherri L. Johnson; Lorien Jasny

2014-01-01

Patterns of social interaction influence how knowledge is generated, communicated, and applied. Theories of social capital and organizational learning suggest that interactions within disciplinary or functional groups foster communication of knowledge, whereas interactions across groups foster generation of new knowledge. We used social network analysis to examine...

Exploring the Peer Interaction Effects on Learning Achievement in a Social Learning Platform Based on Social Network Analysis

ERIC Educational Resources Information Center

Lin, Yu-Tzu; Chen, Ming-Puu; Chang, Chia-Hu; Chang, Pu-Chen

2017-01-01

The benefits of social learning have been recognized by existing research. To explore knowledge distribution in social learning and its effects on learning achievement, we developed a social learning platform and explored students' behaviors of peer interactions by the proposed algorithms based on social network analysis. An empirical study was…

Review: visual analytics of climate networks

NASA Astrophysics Data System (ADS)

Nocke, T.; Buschmann, S.; Donges, J. F.; Marwan, N.; Schulz, H.-J.; Tominski, C.

2015-09-01

Network analysis has become an important approach in studying complex spatiotemporal behaviour within geophysical observation and simulation data. This new field produces increasing numbers of large geo-referenced networks to be analysed. Particular focus lies currently on the network analysis of the complex statistical interrelationship structure within climatological fields. The standard procedure for such network analyses is the extraction of network measures in combination with static standard visualisation methods. Existing interactive visualisation methods and tools for geo-referenced network exploration are often either not known to the analyst or their potential is not fully exploited. To fill this gap, we illustrate how interactive visual analytics methods in combination with geovisualisation can be tailored for visual climate network investigation. Therefore, the paper provides a problem analysis relating the multiple visualisation challenges to a survey undertaken with network analysts from the research fields of climate and complex systems science. Then, as an overview for the interested practitioner, we review the state-of-the-art in climate network visualisation and provide an overview of existing tools. As a further contribution, we introduce the visual network analytics tools CGV and GTX, providing tailored solutions for climate network analysis, including alternative geographic projections, edge bundling, and 3-D network support. Using these tools, the paper illustrates the application potentials of visual analytics for climate networks based on several use cases including examples from global, regional, and multi-layered climate networks.

Review: visual analytics of climate networks

NASA Astrophysics Data System (ADS)

Nocke, T.; Buschmann, S.; Donges, J. F.; Marwan, N.; Schulz, H.-J.; Tominski, C.

2015-04-01

Network analysis has become an important approach in studying complex spatiotemporal behaviour within geophysical observation and simulation data. This new field produces increasing amounts of large geo-referenced networks to be analysed. Particular focus lies currently on the network analysis of the complex statistical interrelationship structure within climatological fields. The standard procedure for such network analyses is the extraction of network measures in combination with static standard visualisation methods. Existing interactive visualisation methods and tools for geo-referenced network exploration are often either not known to the analyst or their potential is not fully exploited. To fill this gap, we illustrate how interactive visual analytics methods in combination with geovisualisation can be tailored for visual climate network investigation. Therefore, the paper provides a problem analysis, relating the multiple visualisation challenges with a survey undertaken with network analysts from the research fields of climate and complex systems science. Then, as an overview for the interested practitioner, we review the state-of-the-art in climate network visualisation and provide an overview of existing tools. As a further contribution, we introduce the visual network analytics tools CGV and GTX, providing tailored solutions for climate network analysis, including alternative geographic projections, edge bundling, and 3-D network support. Using these tools, the paper illustrates the application potentials of visual analytics for climate networks based on several use cases including examples from global, regional, and multi-layered climate networks.

Optimization of neural network architecture using genetic programming improves detection and modeling of gene-gene interactions in studies of human diseases

PubMed Central

Ritchie, Marylyn D; White, Bill C; Parker, Joel S; Hahn, Lance W; Moore, Jason H

2003-01-01

Background Appropriate definition of neural network architecture prior to data analysis is crucial for successful data mining. This can be challenging when the underlying model of the data is unknown. The goal of this study was to determine whether optimizing neural network architecture using genetic programming as a machine learning strategy would improve the ability of neural networks to model and detect nonlinear interactions among genes in studies of common human diseases. Results Using simulated data, we show that a genetic programming optimized neural network approach is able to model gene-gene interactions as well as a traditional back propagation neural network. Furthermore, the genetic programming optimized neural network is better than the traditional back propagation neural network approach in terms of predictive ability and power to detect gene-gene interactions when non-functional polymorphisms are present. Conclusion This study suggests that a machine learning strategy for optimizing neural network architecture may be preferable to traditional trial-and-error approaches for the identification and characterization of gene-gene interactions in common, complex human diseases. PMID:12846935

Effect of Field Spread on Resting-State Magneto Encephalography Functional Network Analysis: A Computational Modeling Study.

PubMed

Silva Pereira, Silvana; Hindriks, Rikkert; Mühlberg, Stefanie; Maris, Eric; van Ede, Freek; Griffa, Alessandra; Hagmann, Patric; Deco, Gustavo

2017-11-01

A popular way to analyze resting-state electroencephalography (EEG) and magneto encephalography (MEG) data is to treat them as a functional network in which sensors are identified with nodes and the interaction between channel time series and the network connections. Although conceptually appealing, the network-theoretical approach to sensor-level EEG and MEG data is challenged by the fact that EEG and MEG time series are mixtures of source activity. It is, therefore, of interest to assess the relationship between functional networks of source activity and the ensuing sensor-level networks. Since these topological features are of high interest in experimental studies, we address the question of to what extent the network topology can be reconstructed from sensor-level functional connectivity (FC) measures in case of MEG data. Simple simulations that consider only a small number of regions do not allow to assess network properties; therefore, we use a diffusion magnetic resonance imaging-constrained whole-brain computational model of resting-state activity. Our motivation lies behind the fact that still many contributions found in the literature perform network analysis at sensor level, and we aim at showing the discrepancies between source- and sensor-level network topologies by using realistic simulations of resting-state cortical activity. Our main findings are that the effect of field spread on network topology depends on the type of interaction (instantaneous or lagged) and leads to an underestimation of lagged FC at sensor level due to instantaneous mixing of cortical signals, instantaneous interaction is more sensitive to field spread than lagged interaction, and discrepancies are reduced when using planar gradiometers rather than axial gradiometers. We, therefore, recommend using lagged interaction measures on planar gradiometer data when investigating network properties of resting-state sensor-level MEG data.

Yeast Phenomics: An Experimental Approach for Modeling Gene Interaction Networks that Buffer Disease

PubMed Central

Hartman, John L.; Stisher, Chandler; Outlaw, Darryl A.; Guo, Jingyu; Shah, Najaf A.; Tian, Dehua; Santos, Sean M.; Rodgers, John W.; White, Richard A.

2015-01-01

The genome project increased appreciation of genetic complexity underlying disease phenotypes: many genes contribute each phenotype and each gene contributes multiple phenotypes. The aspiration of predicting common disease in individuals has evolved from seeking primary loci to marginal risk assignments based on many genes. Genetic interaction, defined as contributions to a phenotype that are dependent upon particular digenic allele combinations, could improve prediction of phenotype from complex genotype, but it is difficult to study in human populations. High throughput, systematic analysis of S. cerevisiae gene knockouts or knockdowns in the context of disease-relevant phenotypic perturbations provides a tractable experimental approach to derive gene interaction networks, in order to deduce by cross-species gene homology how phenotype is buffered against disease-risk genotypes. Yeast gene interaction network analysis to date has revealed biology more complex than previously imagined. This has motivated the development of more powerful yeast cell array phenotyping methods to globally model the role of gene interaction networks in modulating phenotypes (which we call yeast phenomic analysis). The article illustrates yeast phenomic technology, which is applied here to quantify gene X media interaction at higher resolution and supports use of a human-like media for future applications of yeast phenomics for modeling human disease. PMID:25668739

Microbial interaction networks in soil and in silico

NASA Astrophysics Data System (ADS)

Vetsigian, Kalin

2012-02-01

Soil harbors a huge number of microbial species interacting through secretion of antibiotics and other chemicals. What patterns of species interactions allow for this astonishing biodiversity to be sustained, and how do these interactions evolve? I used a combined experimental-theoretical approach to tackle these questions. Focusing on bacteria from the genus Steptomyces, known for their diverse secondary metabolism, I isolated 64 natural strains from several individual grains of soil and systematically measured all pairwise interactions among them. Quantitative measurements on such scale were enabled by a novel experimental platform based on robotic handling, a custom scanner array and automatic image analysis. This unique platform allowed the simultaneous capturing of ˜15,000 time-lapse movies of growing colonies of each isolate on media conditioned by each of the other isolates. The data revealed a rich network of strong negative (inhibitory) and positive (stimulating) interactions. Analysis of this network and the phylogeny of the isolates, together with mathematical modeling of microbial communities, revealed that: 1) The network of interactions has three special properties: ``balance'', ``bi- modality'' and ``reciprocity''; 2) The interaction network is fast evolving; 3) Mathematical modeling explains how rapid evolution can give rise to the three special properties through an interplay between ecology and evolution. These properties are not a result of stable co-existence, but rather of continuous evolutionary turnover of strains with different production and resistance capabilities.

A novel method to identify hub pathways of rheumatoid arthritis based on differential pathway networks.

PubMed

Wei, Shi-Tong; Sun, Yong-Hua; Zong, Shi-Hua

2017-09-01

The aim of the current study was to identify hub pathways of rheumatoid arthritis (RA) using a novel method based on differential pathway network (DPN) analysis. The present study proposed a DPN where protein‑protein interaction (PPI) network was integrated with pathway‑pathway interactions. Pathway data was obtained from background PPI network and the Reactome pathway database. Subsequently, pathway interactions were extracted from the pathway data by building randomized gene‑gene interactions and a weight value was assigned to each pathway interaction using Spearman correlation coefficient (SCC) to identify differential pathway interactions. Differential pathway interactions were visualized using Cytoscape to construct a DPN. Topological analysis was conducted to identify hub pathways that possessed the top 5% degree distribution of DPN. Modules of DPN were mined according to ClusterONE. A total of 855 pathways were selected to build pathway interactions. By filtrating pathway interactions of weight values >0.7, a DPN with 312 nodes and 791 edges was obtained. Topological degree analysis revealed 15 hub pathways, such as heparan sulfate/heparin‑glycosaminoglycan (HS‑GAG) degradation, HS‑GAG metabolism and keratan sulfate degradation for RA based on DPN. Furthermore, hub pathways were also important in modules, which validated the significance of hub pathways. In conclusion, the proposed method is a computationally efficient way to identify hub pathways of RA, which identified 15 hub pathways that may be potential biomarkers and provide insight to future investigation and treatment of RA.

Protein complexes, big data, machine learning and integrative proteomics: lessons learned over a decade of systematic analysis of protein interaction networks.

PubMed

Havugimana, Pierre C; Hu, Pingzhao; Emili, Andrew

2017-10-01

Elucidation of the networks of physical (functional) interactions present in cells and tissues is fundamental for understanding the molecular organization of biological systems, the mechanistic basis of essential and disease-related processes, and for functional annotation of previously uncharacterized proteins (via guilt-by-association or -correlation). After a decade in the field, we felt it timely to document our own experiences in the systematic analysis of protein interaction networks. Areas covered: Researchers worldwide have contributed innovative experimental and computational approaches that have driven the rapidly evolving field of 'functional proteomics'. These include mass spectrometry-based methods to characterize macromolecular complexes on a global-scale and sophisticated data analysis tools - most notably machine learning - that allow for the generation of high-quality protein association maps. Expert commentary: Here, we recount some key lessons learned, with an emphasis on successful workflows, and challenges, arising from our own and other groups' ongoing efforts to generate, interpret and report proteome-scale interaction networks in increasingly diverse biological contexts.

Network Configurations in the Human Brain Reflect Choice Bias during Rapid Face Processing.

PubMed

Tu, Tao; Schneck, Noam; Muraskin, Jordan; Sajda, Paul

2017-12-13

Network interactions are likely to be instrumental in processes underlying rapid perception and cognition. Specifically, high-level and perceptual regions must interact to balance pre-existing models of the environment with new incoming stimuli. Simultaneous electroencephalography (EEG) and fMRI (EEG/fMRI) enables temporal characterization of brain-network interactions combined with improved anatomical localization of regional activity. In this paper, we use simultaneous EEG/fMRI and multivariate dynamical systems (MDS) analysis to characterize network relationships between constitute brain areas that reflect a subject's choice for a face versus nonface categorization task. Our simultaneous EEG and fMRI analysis on 21 human subjects (12 males, 9 females) identifies early perceptual and late frontal subsystems that are selective to the categorical choice of faces versus nonfaces. We analyze the interactions between these subsystems using an MDS in the space of the BOLD signal. Our main findings show that differences between face-choice and house-choice networks are seen in the network interactions between the early and late subsystems, and that the magnitude of the difference in network interaction positively correlates with the behavioral false-positive rate of face choices. We interpret this to reflect the role of saliency and expectations likely encoded in frontal "late" regions on perceptual processes occurring in "early" perceptual regions. SIGNIFICANCE STATEMENT Our choices are affected by our biases. In visual perception and cognition such biases can be commonplace and quite curious-e.g., we see a human face when staring up at a cloud formation or down at a piece of toast at the breakfast table. Here we use multimodal neuroimaging and dynamical systems analysis to measure whole-brain spatiotemporal dynamics while subjects make decisions regarding the type of object they see in rapidly flashed images. We find that the degree of interaction in these networks accounts for a substantial fraction of our bias to see faces. In general, our findings illustrate how the properties of spatiotemporal networks yield insight into the mechanisms of how we form decisions. Copyright © 2017 the authors 0270-6474/17/3712226-12$15.00/0.

Network Configurations in the Human Brain Reflect Choice Bias during Rapid Face Processing

PubMed Central

Schneck, Noam

2017-01-01

Network interactions are likely to be instrumental in processes underlying rapid perception and cognition. Specifically, high-level and perceptual regions must interact to balance pre-existing models of the environment with new incoming stimuli. Simultaneous electroencephalography (EEG) and fMRI (EEG/fMRI) enables temporal characterization of brain–network interactions combined with improved anatomical localization of regional activity. In this paper, we use simultaneous EEG/fMRI and multivariate dynamical systems (MDS) analysis to characterize network relationships between constitute brain areas that reflect a subject's choice for a face versus nonface categorization task. Our simultaneous EEG and fMRI analysis on 21 human subjects (12 males, 9 females) identifies early perceptual and late frontal subsystems that are selective to the categorical choice of faces versus nonfaces. We analyze the interactions between these subsystems using an MDS in the space of the BOLD signal. Our main findings show that differences between face-choice and house-choice networks are seen in the network interactions between the early and late subsystems, and that the magnitude of the difference in network interaction positively correlates with the behavioral false-positive rate of face choices. We interpret this to reflect the role of saliency and expectations likely encoded in frontal “late” regions on perceptual processes occurring in “early” perceptual regions. SIGNIFICANCE STATEMENT Our choices are affected by our biases. In visual perception and cognition such biases can be commonplace and quite curious—e.g., we see a human face when staring up at a cloud formation or down at a piece of toast at the breakfast table. Here we use multimodal neuroimaging and dynamical systems analysis to measure whole-brain spatiotemporal dynamics while subjects make decisions regarding the type of object they see in rapidly flashed images. We find that the degree of interaction in these networks accounts for a substantial fraction of our bias to see faces. In general, our findings illustrate how the properties of spatiotemporal networks yield insight into the mechanisms of how we form decisions. PMID:29118108

Structural stability of interaction networks against negative external fields

NASA Astrophysics Data System (ADS)

Yoon, S.; Goltsev, A. V.; Mendes, J. F. F.

2018-04-01

We explore structural stability of weighted and unweighted networks of positively interacting agents against a negative external field. We study how the agents support the activity of each other to confront the negative field, which suppresses the activity of agents and can lead to collapse of the whole network. The competition between the interactions and the field shape the structure of stable states of the system. In unweighted networks (uniform interactions) the stable states have the structure of k -cores of the interaction network. The interplay between the topology and the distribution of weights (heterogeneous interactions) impacts strongly the structural stability against a negative field, especially in the case of fat-tailed distributions of weights. We show that apart from critical slowing down there is also a critical change in the system structure that precedes the network collapse. The change can serve as an early warning of the critical transition. To characterize changes of network structure we develop a method based on statistical analysis of the k -core organization and so-called "corona" clusters belonging to the k -cores.

Social patterns revealed through random matrix theory

NASA Astrophysics Data System (ADS)

Sarkar, Camellia; Jalan, Sarika

2014-11-01

Despite the tremendous advancements in the field of network theory, very few studies have taken weights in the interactions into consideration that emerge naturally in all real-world systems. Using random matrix analysis of a weighted social network, we demonstrate the profound impact of weights in interactions on emerging structural properties. The analysis reveals that randomness existing in particular time frame affects the decisions of individuals rendering them more freedom of choice in situations of financial security. While the structural organization of networks remains the same throughout all datasets, random matrix theory provides insight into the interaction pattern of individuals of the society in situations of crisis. It has also been contemplated that individual accountability in terms of weighted interactions remains as a key to success unless segregation of tasks comes into play.

Construction and analysis of gene-gene dynamics influence networks based on a Boolean model.

PubMed

Mazaya, Maulida; Trinh, Hung-Cuong; Kwon, Yung-Keun

2017-12-21

Identification of novel gene-gene relations is a crucial issue to understand system-level biological phenomena. To this end, many methods based on a correlation analysis of gene expressions or structural analysis of molecular interaction networks have been proposed. They have a limitation in identifying more complicated gene-gene dynamical relations, though. To overcome this limitation, we proposed a measure to quantify a gene-gene dynamical influence (GDI) using a Boolean network model and constructed a GDI network to indicate existence of a dynamical influence for every ordered pair of genes. It represents how much a state trajectory of a target gene is changed by a knockout mutation subject to a source gene in a gene-gene molecular interaction (GMI) network. Through a topological comparison between GDI and GMI networks, we observed that the former network is denser than the latter network, which implies that there exist many gene pairs of dynamically influencing but molecularly non-interacting relations. In addition, a larger number of hub genes were generated in the GDI network. On the other hand, there was a correlation between these networks such that the degree value of a node was positively correlated to each other. We further investigated the relationships of the GDI value with structural properties and found that there are negative and positive correlations with the length of a shortest path and the number of paths, respectively. In addition, a GDI network could predict a set of genes whose steady-state expression is affected in E. coli gene-knockout experiments. More interestingly, we found that the drug-targets with side-effects have a larger number of outgoing links than the other genes in the GDI network, which implies that they are more likely to influence the dynamics of other genes. Finally, we found biological evidences showing that the gene pairs which are not molecularly interacting but dynamically influential can be considered for novel gene-gene relationships. Taken together, construction and analysis of the GDI network can be a useful approach to identify novel gene-gene relationships in terms of the dynamical influence.

Causal functional contributions and interactions in the attention network of the brain: an objective multi-perturbation analysis.

PubMed

Zavaglia, Melissa; Hilgetag, Claus C

2016-06-01

Spatial attention is a prime example for the distributed network functions of the brain. Lesion studies in animal models have been used to investigate intact attentional mechanisms as well as perspectives for rehabilitation in the injured brain. Here, we systematically analyzed behavioral data from cooling deactivation and permanent lesion experiments in the cat, where unilateral deactivation of the posterior parietal cortex (in the vicinity of the posterior middle suprasylvian cortex, pMS) or the superior colliculus (SC) cause a severe neglect in the contralateral hemifield. Counterintuitively, additional deactivation of structures in the opposite hemisphere reverses the deficit. Using such lesion data, we employed a game-theoretical approach, multi-perturbation Shapley value analysis (MSA), for inferring functional contributions and network interactions of bilateral pMS and SC from behavioral performance in visual attention studies. The approach provides an objective theoretical strategy for lesion inferences and allows a unique quantitative characterization of regional functional contributions and interactions on the basis of multi-perturbations. The quantitative analysis demonstrated that right posterior parietal cortex and superior colliculus made the strongest positive contributions to left-field orienting, while left brain regions had negative contributions, implying that their perturbation may reverse the effects of contralateral lesions or improve normal function. An analysis of functional modulations and interactions among the regions revealed redundant interactions (implying functional overlap) between regions within each hemisphere, and synergistic interactions between bilateral regions. To assess the reliability of the MSA method in the face of variable and incomplete input data, we performed a sensitivity analysis, investigating how much the contribution values of the four regions depended on the performance of specific configurations and on the prediction of unknown performances. The results suggest that the MSA approach is sensitive to categorical, but insensitive to gradual changes in the input data. Finally, we created a basic network model that was based on the known anatomical interactions among cortical-tectal regions and reproduced the experimentally observed behavior in visual orienting. We discuss the structural organization of the network model relative to the causal modulations identified by MSA, to aid a mechanistic understanding of the attention network of the brain.

Identification of fever and vaccine-associated gene interaction networks using ontology-based literature mining

PubMed Central

2012-01-01

Background Fever is one of the most common adverse events of vaccines. The detailed mechanisms of fever and vaccine-associated gene interaction networks are not fully understood. In the present study, we employed a genome-wide, Centrality and Ontology-based Network Discovery using Literature data (CONDL) approach to analyse the genes and gene interaction networks associated with fever or vaccine-related fever responses. Results Over 170,000 fever-related articles from PubMed abstracts and titles were retrieved and analysed at the sentence level using natural language processing techniques to identify genes and vaccines (including 186 Vaccine Ontology terms) as well as their interactions. This resulted in a generic fever network consisting of 403 genes and 577 gene interactions. A vaccine-specific fever sub-network consisting of 29 genes and 28 gene interactions was extracted from articles that are related to both fever and vaccines. In addition, gene-vaccine interactions were identified. Vaccines (including 4 specific vaccine names) were found to directly interact with 26 genes. Gene set enrichment analysis was performed using the genes in the generated interaction networks. Moreover, the genes in these networks were prioritized using network centrality metrics. Making scientific discoveries and generating new hypotheses were possible by using network centrality and gene set enrichment analyses. For example, our study found that the genes in the generic fever network were more enriched in cell death and responses to wounding, and the vaccine sub-network had more gene enrichment in leukocyte activation and phosphorylation regulation. The most central genes in the vaccine-specific fever network are predicted to be highly relevant to vaccine-induced fever, whereas genes that are central only in the generic fever network are likely to be highly relevant to generic fever responses. Interestingly, no Toll-like receptors (TLRs) were found in the gene-vaccine interaction network. Since multiple TLRs were found in the generic fever network, it is reasonable to hypothesize that vaccine-TLR interactions may play an important role in inducing fever response, which deserves a further investigation. Conclusions This study demonstrated that ontology-based literature mining is a powerful method for analyzing gene interaction networks and generating new scientific hypotheses. PMID:23256563

How can social network analysis contribute to social behavior research in applied ethology?

PubMed

Makagon, Maja M; McCowan, Brenda; Mench, Joy A

2012-05-01

Social network analysis is increasingly used by behavioral ecologists and primatologists to describe the patterns and quality of interactions among individuals. We provide an overview of this methodology, with examples illustrating how it can be used to study social behavior in applied contexts. Like most kinds of social interaction analyses, social network analysis provides information about direct relationships (e.g. dominant-subordinate relationships). However, it also generates a more global model of social organization that determines how individual patterns of social interaction relate to individual and group characteristics. A particular strength of this approach is that it provides standardized mathematical methods for calculating metrics of sociality across levels of social organization, from the population and group levels to the individual level. At the group level these metrics can be used to track changes in social network structures over time, evaluate the effect of the environment on social network structure, or compare social structures across groups, populations or species. At the individual level, the metrics allow quantification of the heterogeneity of social experience within groups and identification of individuals who may play especially important roles in maintaining social stability or information flow throughout the network.

Using Social Network Measures in Wildlife Disease Ecology, Epidemiology, and Management

PubMed Central

Silk, Matthew J.; Croft, Darren P.; Delahay, Richard J.; Hodgson, David J.; Boots, Mike; Weber, Nicola; McDonald, Robbie A.

2017-01-01

Abstract Contact networks, behavioral interactions, and shared use of space can all have important implications for the spread of disease in animals. Social networks enable the quantification of complex patterns of interactions; therefore, network analysis is becoming increasingly widespread in the study of infectious disease in animals, including wildlife. We present an introductory guide to using social-network-analytical approaches in wildlife disease ecology, epidemiology, and management. We focus on providing detailed practical guidance for the use of basic descriptive network measures by suggesting the research questions to which each technique is best suited and detailing the software available for each. We also discuss how using network approaches can be used beyond the study of social contacts and across a range of spatial and temporal scales. Finally, we integrate these approaches to examine how network analysis can be used to inform the implementation and monitoring of effective disease management strategies. PMID:28596616

Modeling and simulating networks of interdependent protein interactions.

PubMed

Stöcker, Bianca K; Köster, Johannes; Zamir, Eli; Rahmann, Sven

2018-05-21

Protein interactions are fundamental building blocks of biochemical reaction systems underlying cellular functions. The complexity and functionality of these systems emerge not only from the protein interactions themselves but also from the dependencies between these interactions, as generated by allosteric effects or mutual exclusion due to steric hindrance. Therefore, formal models for integrating and utilizing information about interaction dependencies are of high interest. Here, we describe an approach for endowing protein networks with interaction dependencies using propositional logic, thereby obtaining constrained protein interaction networks ("constrained networks"). The construction of these networks is based on public interaction databases as well as text-mined information about interaction dependencies. We present an efficient data structure and algorithm to simulate protein complex formation in constrained networks. The efficiency of the model allows fast simulation and facilitates the analysis of many proteins in large networks. In addition, this approach enables the simulation of perturbation effects, such as knockout of single or multiple proteins and changes of protein concentrations. We illustrate how our model can be used to analyze a constrained human adhesome protein network, which is responsible for the formation of diverse and dynamic cell-matrix adhesion sites. By comparing protein complex formation under known interaction dependencies versus without dependencies, we investigate how these dependencies shape the resulting repertoire of protein complexes. Furthermore, our model enables investigating how the interplay of network topology with interaction dependencies influences the propagation of perturbation effects across a large biochemical system. Our simulation software CPINSim (for Constrained Protein Interaction Network Simulator) is available under the MIT license at http://github.com/BiancaStoecker/cpinsim and as a Bioconda package (https://bioconda.github.io).

Gene essentiality and the topology of protein interaction networks

PubMed Central

Coulomb, Stéphane; Bauer, Michel; Bernard, Denis; Marsolier-Kergoat, Marie-Claude

2005-01-01

The mechanistic bases for gene essentiality and for cell mutational resistance have long been disputed. The recent availability of large protein interaction databases has fuelled the analysis of protein interaction networks and several authors have proposed that gene dispensability could be strongly related to some topological parameters of these networks. However, many results were based on protein interaction data whose biases were not taken into account. In this article, we show that the essentiality of a gene in yeast is poorly related to the number of interactants (or degree) of the corresponding protein and that the physiological consequences of gene deletions are unrelated to several other properties of proteins in the interaction networks, such as the average degrees of their nearest neighbours, their clustering coefficients or their relative distances. We also found that yeast protein interaction networks lack degree correlation, i.e. a propensity for their vertices to associate according to their degrees. Gene essentiality and more generally cell resistance against mutations thus seem largely unrelated to many parameters of protein network topology. PMID:16087428

Molecular ecological network analyses.

PubMed

Deng, Ye; Jiang, Yi-Huei; Yang, Yunfeng; He, Zhili; Luo, Feng; Zhou, Jizhong

2012-05-30

Understanding the interaction among different species within a community and their responses to environmental changes is a central goal in ecology. However, defining the network structure in a microbial community is very challenging due to their extremely high diversity and as-yet uncultivated status. Although recent advance of metagenomic technologies, such as high throughout sequencing and functional gene arrays, provide revolutionary tools for analyzing microbial community structure, it is still difficult to examine network interactions in a microbial community based on high-throughput metagenomics data. Here, we describe a novel mathematical and bioinformatics framework to construct ecological association networks named molecular ecological networks (MENs) through Random Matrix Theory (RMT)-based methods. Compared to other network construction methods, this approach is remarkable in that the network is automatically defined and robust to noise, thus providing excellent solutions to several common issues associated with high-throughput metagenomics data. We applied it to determine the network structure of microbial communities subjected to long-term experimental warming based on pyrosequencing data of 16 S rRNA genes. We showed that the constructed MENs under both warming and unwarming conditions exhibited topological features of scale free, small world and modularity, which were consistent with previously described molecular ecological networks. Eigengene analysis indicated that the eigengenes represented the module profiles relatively well. In consistency with many other studies, several major environmental traits including temperature and soil pH were found to be important in determining network interactions in the microbial communities examined. To facilitate its application by the scientific community, all these methods and statistical tools have been integrated into a comprehensive Molecular Ecological Network Analysis Pipeline (MENAP), which is open-accessible now (http://ieg2.ou.edu/MENA). The RMT-based molecular ecological network analysis provides powerful tools to elucidate network interactions in microbial communities and their responses to environmental changes, which are fundamentally important for research in microbial ecology and environmental microbiology.

Cooperative spreading processes in multiplex networks.

PubMed

Wei, Xiang; Chen, Shihua; Wu, Xiaoqun; Ning, Di; Lu, Jun-An

2016-06-01

This study is concerned with the dynamic behaviors of epidemic spreading in multiplex networks. A model composed of two interacting complex networks is proposed to describe cooperative spreading processes, wherein the virus spreading in one layer can penetrate into the other to promote the spreading process. The global epidemic threshold of the model is smaller than the epidemic thresholds of the corresponding isolated networks. Thus, global epidemic onset arises in the interacting networks even though an epidemic onset does not arise in each isolated network. Simulations verify the analysis results and indicate that cooperative spreading processes in multiplex networks enhance the final infection fraction.

Hamiltonian dynamics for complex food webs

NASA Astrophysics Data System (ADS)

Kozlov, Vladimir; Vakulenko, Sergey; Wennergren, Uno

2016-03-01

We investigate stability and dynamics of large ecological networks by introducing classical methods of dynamical system theory from physics, including Hamiltonian and averaging methods. Our analysis exploits the topological structure of the network, namely the existence of strongly connected nodes (hubs) in the networks. We reveal new relations between topology, interaction structure, and network dynamics. We describe mechanisms of catastrophic phenomena leading to sharp changes of dynamics and hence completely altering the ecosystem. We also show how these phenomena depend on the structure of interaction between species. We can conclude that a Hamiltonian structure of biological interactions leads to stability and large biodiversity.

A Social Network Analysis of Teaching and Research Collaboration in a Teachers' Virtual Learning Community

ERIC Educational Resources Information Center

Lin, Xiaofan; Hu, Xiaoyong; Hu, Qintai; Liu, Zhichun

2016-01-01

Analysing the structure of a social network can help us understand the key factors influencing interaction and collaboration in a virtual learning community (VLC). Here, we describe the mechanisms used in social network analysis (SNA) to analyse the social network structure of a VLC for teachers and discuss the relationship between face-to-face…

Empirical Comparison of Visualization Tools for Larger-Scale Network Analysis

DOE PAGES

Pavlopoulos, Georgios A.; Paez-Espino, David; Kyrpides, Nikos C.; ...

2017-07-18

Gene expression, signal transduction, protein/chemical interactions, biomedical literature cooccurrences, and other concepts are often captured in biological network representations where nodes represent a certain bioentity and edges the connections between them. While many tools to manipulate, visualize, and interactively explore such networks already exist, only few of them can scale up and follow today’s indisputable information growth. In this review, we shortly list a catalog of available network visualization tools and, from a user-experience point of view, we identify four candidate tools suitable for larger-scale network analysis, visualization, and exploration. Lastly, we comment on their strengths and their weaknesses andmore » empirically discuss their scalability, user friendliness, and postvisualization capabilities.« less

Empirical Comparison of Visualization Tools for Larger-Scale Network Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pavlopoulos, Georgios A.; Paez-Espino, David; Kyrpides, Nikos C.

Gene expression, signal transduction, protein/chemical interactions, biomedical literature cooccurrences, and other concepts are often captured in biological network representations where nodes represent a certain bioentity and edges the connections between them. While many tools to manipulate, visualize, and interactively explore such networks already exist, only few of them can scale up and follow today’s indisputable information growth. In this review, we shortly list a catalog of available network visualization tools and, from a user-experience point of view, we identify four candidate tools suitable for larger-scale network analysis, visualization, and exploration. Lastly, we comment on their strengths and their weaknesses andmore » empirically discuss their scalability, user friendliness, and postvisualization capabilities.« less

FACETS: multi-faceted functional decomposition of protein interaction networks.

PubMed

Seah, Boon-Siew; Bhowmick, Sourav S; Dewey, C Forbes

2012-10-15

The availability of large-scale curated protein interaction datasets has given rise to the opportunity to investigate higher level organization and modularity within the protein-protein interaction (PPI) network using graph theoretic analysis. Despite the recent progress, systems level analysis of high-throughput PPIs remains a daunting task because of the amount of data they present. In this article, we propose a novel PPI network decomposition algorithm called FACETS in order to make sense of the deluge of interaction data using Gene Ontology (GO) annotations. FACETS finds not just a single functional decomposition of the PPI network, but a multi-faceted atlas of functional decompositions that portray alternative perspectives of the functional landscape of the underlying PPI network. Each facet in the atlas represents a distinct interpretation of how the network can be functionally decomposed and organized. Our algorithm maximizes interpretative value of the atlas by optimizing inter-facet orthogonality and intra-facet cluster modularity. We tested our algorithm on the global networks from IntAct, and compared it with gold standard datasets from MIPS and KEGG. We demonstrated the performance of FACETS. We also performed a case study that illustrates the utility of our approach. Supplementary data are available at the Bioinformatics online. Our software is available freely for non-commercial purposes from: http://www.cais.ntu.edu.sg/~assourav/Facets/

Protein-protein interaction networks identify targets which rescue the MPP+ cellular model of Parkinson’s disease

NASA Astrophysics Data System (ADS)

Keane, Harriet; Ryan, Brent J.; Jackson, Brendan; Whitmore, Alan; Wade-Martins, Richard

2015-11-01

Neurodegenerative diseases are complex multifactorial disorders characterised by the interplay of many dysregulated physiological processes. As an exemplar, Parkinson’s disease (PD) involves multiple perturbed cellular functions, including mitochondrial dysfunction and autophagic dysregulation in preferentially-sensitive dopamine neurons, a selective pathophysiology recapitulated in vitro using the neurotoxin MPP+. Here we explore a network science approach for the selection of therapeutic protein targets in the cellular MPP+ model. We hypothesised that analysis of protein-protein interaction networks modelling MPP+ toxicity could identify proteins critical for mediating MPP+ toxicity. Analysis of protein-protein interaction networks constructed to model the interplay of mitochondrial dysfunction and autophagic dysregulation (key aspects of MPP+ toxicity) enabled us to identify four proteins predicted to be key for MPP+ toxicity (P62, GABARAP, GBRL1 and GBRL2). Combined, but not individual, knockdown of these proteins increased cellular susceptibility to MPP+ toxicity. Conversely, combined, but not individual, over-expression of the network targets provided rescue of MPP+ toxicity associated with the formation of autophagosome-like structures. We also found that modulation of two distinct proteins in the protein-protein interaction network was necessary and sufficient to mitigate neurotoxicity. Together, these findings validate our network science approach to multi-target identification in complex neurological diseases.

Topological robustness analysis of protein interaction networks reveals key targets for overcoming chemotherapy resistance in glioma

NASA Astrophysics Data System (ADS)

Azevedo, Hátylas; Moreira-Filho, Carlos Alberto

2015-11-01

Biological networks display high robustness against random failures but are vulnerable to targeted attacks on central nodes. Thus, network topology analysis represents a powerful tool for investigating network susceptibility against targeted node removal. Here, we built protein interaction networks associated with chemoresistance to temozolomide, an alkylating agent used in glioma therapy, and analyzed their modular structure and robustness against intentional attack. These networks showed functional modules related to DNA repair, immunity, apoptosis, cell stress, proliferation and migration. Subsequently, network vulnerability was assessed by means of centrality-based attacks based on the removal of node fractions in descending orders of degree, betweenness, or the product of degree and betweenness. This analysis revealed that removing nodes with high degree and high betweenness was more effective in altering networks’ robustness parameters, suggesting that their corresponding proteins may be particularly relevant to target temozolomide resistance. In silico data was used for validation and confirmed that central nodes are more relevant for altering proliferation rates in temozolomide-resistant glioma cell lines and for predicting survival in glioma patients. Altogether, these results demonstrate how the analysis of network vulnerability to topological attack facilitates target prioritization for overcoming cancer chemoresistance.

How the study of online collaborative learning can guide teachers and predict students' performance in a medical course.

PubMed

Saqr, Mohammed; Fors, Uno; Tedre, Matti

2018-02-06

Collaborative learning facilitates reflection, diversifies understanding and stimulates skills of critical and higher-order thinking. Although the benefits of collaborative learning have long been recognized, it is still rarely studied by social network analysis (SNA) in medical education, and the relationship of parameters that can be obtained via SNA with students' performance remains largely unknown. The aim of this work was to assess the potential of SNA for studying online collaborative clinical case discussions in a medical course and to find out which activities correlate with better performance and help predict final grade or explain variance in performance. Interaction data were extracted from the learning management system (LMS) forum module of the Surgery course in Qassim University, College of Medicine. The data were analyzed using social network analysis. The analysis included visual as well as a statistical analysis. Correlation with students' performance was calculated, and automatic linear regression was used to predict students' performance. By using social network analysis, we were able to analyze a large number of interactions in online collaborative discussions and gain an overall insight of the course social structure, track the knowledge flow and the interaction patterns, as well as identify the active participants and the prominent discussion moderators. When augmented with calculated network parameters, SNA offered an accurate view of the course network, each user's position, and level of connectedness. Results from correlation coefficients, linear regression, and logistic regression indicated that a student's position and role in information relay in online case discussions, combined with the strength of that student's network (social capital), can be used as predictors of performance in relevant settings. By using social network analysis, researchers can analyze the social structure of an online course and reveal important information about students' and teachers' interactions that can be valuable in guiding teachers, improve students' engagement, and contribute to learning analytics insights.

Understanding the process of social network evolution: Online-offline integrated analysis of social tie formation

PubMed Central

Kwak, Doyeon

2017-01-01

It is important to consider the interweaving nature of online and offline social networks when we examine social network evolution. However, it is difficult to find any research that examines the process of social tie formation from an integrated perspective. In our study, we quantitatively measure offline interactions and examine the corresponding evolution of online social network in order to understand the significance of interrelationship between online and offline social factors in generating social ties. We analyze the radio signal strength indicator sensor data from a series of social events to understand offline interactions among the participants and measure the structural attributes of their existing online Facebook social networks. By monitoring the changes in their online social networks before and after offline interactions in a series of social events, we verify that the ability to develop an offline interaction into an online friendship is tied to the number of social connections that participants previously had, while the presence of shared mutual friends between a pair of participants disrupts potential new connections within the pre-designed offline social events. Thus, while our integrative approach enables us to confirm the theory of preferential attachment in the process of network formation, the common neighbor theory is not supported. Our dual-dimensional network analysis allows us to observe the actual process of social network evolution rather than to make predictions based on the assumption of self-organizing networks. PMID:28542367

Understanding the process of social network evolution: Online-offline integrated analysis of social tie formation.

PubMed

Kwak, Doyeon; Kim, Wonjoon

2017-01-01

It is important to consider the interweaving nature of online and offline social networks when we examine social network evolution. However, it is difficult to find any research that examines the process of social tie formation from an integrated perspective. In our study, we quantitatively measure offline interactions and examine the corresponding evolution of online social network in order to understand the significance of interrelationship between online and offline social factors in generating social ties. We analyze the radio signal strength indicator sensor data from a series of social events to understand offline interactions among the participants and measure the structural attributes of their existing online Facebook social networks. By monitoring the changes in their online social networks before and after offline interactions in a series of social events, we verify that the ability to develop an offline interaction into an online friendship is tied to the number of social connections that participants previously had, while the presence of shared mutual friends between a pair of participants disrupts potential new connections within the pre-designed offline social events. Thus, while our integrative approach enables us to confirm the theory of preferential attachment in the process of network formation, the common neighbor theory is not supported. Our dual-dimensional network analysis allows us to observe the actual process of social network evolution rather than to make predictions based on the assumption of self-organizing networks.

Classification of functional interactions from multi-electrodes data using conditional modularity analysis

NASA Astrophysics Data System (ADS)

Makhtar, Siti Noormiza; Senik, Mohd Harizal

2018-02-01

The availability of massive amount of neuronal signals are attracting widespread interest in functional connectivity analysis. Functional interactions estimated by multivariate partial coherence analysis in the frequency domain represent the connectivity strength in this study. Modularity is a network measure for the detection of community structure in network analysis. The discovery of community structure for the functional neuronal network was implemented on multi-electrode array (MEA) signals recorded from hippocampal regions in isoflurane-anaesthetized Lister-hooded rats. The analysis is expected to show modularity changes before and after local unilateral kainic acid (KA)-induced epileptiform activity. The result is presented using color-coded graphic of conditional modularity measure for 19 MEA nodes. This network is separated into four sub-regions to show the community detection within each sub-region. The results show that classification of neuronal signals into the inter- and intra-modular nodes is feasible using conditional modularity analysis. Estimation of segregation properties using conditional modularity analysis may provide further information about functional connectivity from MEA data.

Social Network Behavior and Engagement Within a Smoking Cessation Facebook Page.

PubMed

Cole-Lewis, Heather; Perotte, Adler; Galica, Kasia; Dreyer, Lindy; Griffith, Christopher; Schwarz, Mary; Yun, Christopher; Patrick, Heather; Coa, Kisha; Augustson, Erik

2016-08-02

Social media platforms are increasingly being used to support individuals in behavior change attempts, including smoking cessation. Examining the interactions of participants in health-related social media groups can help inform our understanding of how these groups can best be leveraged to facilitate behavior change. The aim of this study was to analyze patterns of participation, self-reported smoking cessation length, and interactions within the National Cancer Institutes' Facebook community for smoking cessation support. Our sample consisted of approximately 4243 individuals who interacted (eg, posted, commented) on the public Smokefree Women Facebook page during the time of data collection. In Phase 1, social network visualizations and centrality measures were used to evaluate network structure and engagement. In Phase 2, an inductive, thematic qualitative content analysis was conducted with a subsample of 500 individuals, and correlational analysis was used to determine how participant engagement was associated with self-reported session length. Between February 2013 and March 2014, there were 875 posts and 4088 comments from approximately 4243 participants. Social network visualizations revealed the moderator's role in keeping the community together and distributing the most active participants. Correlation analyses suggest that engagement in the network was significantly inversely associated with cessation status (Spearman correlation coefficient = -0.14, P=.03, N=243). The content analysis of 1698 posts from 500 randomly selected participants identified the most frequent interactions in the community as providing support (43%, n=721) and announcing number of days smoke free (41%, n=689). These findings highlight the importance of the moderator for network engagement and provide helpful insights into the patterns and types of interactions participants are engaging in. This study adds knowledge of how the social network of a smoking cessation community behaves within the confines of a Facebook group.

JDINAC: joint density-based non-parametric differential interaction network analysis and classification using high-dimensional sparse omics data.

PubMed

Ji, Jiadong; He, Di; Feng, Yang; He, Yong; Xue, Fuzhong; Xie, Lei

2017-10-01

A complex disease is usually driven by a number of genes interwoven into networks, rather than a single gene product. Network comparison or differential network analysis has become an important means of revealing the underlying mechanism of pathogenesis and identifying clinical biomarkers for disease classification. Most studies, however, are limited to network correlations that mainly capture the linear relationship among genes, or rely on the assumption of a parametric probability distribution of gene measurements. They are restrictive in real application. We propose a new Joint density based non-parametric Differential Interaction Network Analysis and Classification (JDINAC) method to identify differential interaction patterns of network activation between two groups. At the same time, JDINAC uses the network biomarkers to build a classification model. The novelty of JDINAC lies in its potential to capture non-linear relations between molecular interactions using high-dimensional sparse data as well as to adjust confounding factors, without the need of the assumption of a parametric probability distribution of gene measurements. Simulation studies demonstrate that JDINAC provides more accurate differential network estimation and lower classification error than that achieved by other state-of-the-art methods. We apply JDINAC to a Breast Invasive Carcinoma dataset, which includes 114 patients who have both tumor and matched normal samples. The hub genes and differential interaction patterns identified were consistent with existing experimental studies. Furthermore, JDINAC discriminated the tumor and normal sample with high accuracy by virtue of the identified biomarkers. JDINAC provides a general framework for feature selection and classification using high-dimensional sparse omics data. R scripts available at https://github.com/jijiadong/JDINAC. lxie@iscb.org. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Network organization of the human autophagy system.

PubMed

Behrends, Christian; Sowa, Mathew E; Gygi, Steven P; Harper, J Wade

2010-07-01

Autophagy, the process by which proteins and organelles are sequestered in autophagosomal vesicles and delivered to the lysosome/vacuole for degradation, provides a primary route for turnover of stable and defective cellular proteins. Defects in this system are linked with numerous human diseases. Although conserved protein kinase, lipid kinase and ubiquitin-like protein conjugation subnetworks controlling autophagosome formation and cargo recruitment have been defined, our understanding of the global organization of this system is limited. Here we report a proteomic analysis of the autophagy interaction network in human cells under conditions of ongoing (basal) autophagy, revealing a network of 751 interactions among 409 candidate interacting proteins with extensive connectivity among subnetworks. Many new autophagy interaction network components have roles in vesicle trafficking, protein or lipid phosphorylation and protein ubiquitination, and affect autophagosome number or flux when depleted by RNA interference. The six ATG8 orthologues in humans (MAP1LC3/GABARAP proteins) interact with a cohort of 67 proteins, with extensive binding partner overlap between family members, and frequent involvement of a conserved surface on ATG8 proteins known to interact with LC3-interacting regions in partner proteins. These studies provide a global view of the mammalian autophagy interaction landscape and a resource for mechanistic analysis of this critical protein homeostasis pathway.

Major component analysis of dynamic networks of physiologic organ interactions

NASA Astrophysics Data System (ADS)

Liu, Kang K. L.; Bartsch, Ronny P.; Ma, Qianli D. Y.; Ivanov, Plamen Ch

2015-09-01

The human organism is a complex network of interconnected organ systems, where the behavior of one system affects the dynamics of other systems. Identifying and quantifying dynamical networks of diverse physiologic systems under varied conditions is a challenge due to the complexity in the output dynamics of the individual systems and the transient and nonlinear characteristics of their coupling. We introduce a novel computational method based on the concept of time delay stability and major component analysis to investigate how organ systems interact as a network to coordinate their functions. We analyze a large database of continuously recorded multi-channel physiologic signals from healthy young subjects during night-time sleep. We identify a network of dynamic interactions between key physiologic systems in the human organism. Further, we find that each physiologic state is characterized by a distinct network structure with different relative contribution from individual organ systems to the global network dynamics. Specifically, we observe a gradual decrease in the strength of coupling of heart and respiration to the rest of the network with transition from wake to deep sleep, and in contrast, an increased relative contribution to network dynamics from chin and leg muscle tone and eye movement, demonstrating a robust association between network topology and physiologic function.

Heard it through the grapevine: indirect networks and employee creativity.

PubMed

Hirst, Giles; Van Knippenberg, Daan; Zhou, Jing; Quintane, Eric; Zhu, Cherrie

2015-03-01

Social networks can be important sources of information and insights that may spark employee creativity. The cross-fertilization of ideas depends not just on access to information and insights through one's direct network-the people one actually interacts with--but at least as much on access to the indirect network one's direct ties connect one to (i.e., people one does not interact with directly, but with whom one's direct ties interact). We propose that the reach efficiency of this indirect network--its nonredundancy in terms of interconnections--is positively related to individual creativity. To help specify the boundaries of this positive influence of the indirect network, we also explore how many steps removed the indirect network still adds to creativity. In addition, we propose that the efficiency (nonredundancy) of one's direct network is important here, because more efficient direct networks give one access to indirect networks with greater reach efficiency. Our hypotheses were supported in a multilevel analysis of multisource survey data from 223 sales representatives nested within 11 divisions of a Chinese pharmaceutical company. This analysis also showed that the creative benefits of reach efficiency were evident for 3 and 4 degrees of separation but were greatest for indirect ties that depend only on one's direct ties. PsycINFO Database Record (c) 2015 APA, all rights reserved.

Data Imputation in Epistatic MAPs by Network-Guided Matrix Completion

PubMed Central

Žitnik, Marinka; Zupan, Blaž

2015-01-01

Abstract Epistatic miniarray profile (E-MAP) is a popular large-scale genetic interaction discovery platform. E-MAPs benefit from quantitative output, which makes it possible to detect subtle interactions with greater precision. However, due to the limits of biotechnology, E-MAP studies fail to measure genetic interactions for up to 40% of gene pairs in an assay. Missing measurements can be recovered by computational techniques for data imputation, in this way completing the interaction profiles and enabling downstream analysis algorithms that could otherwise be sensitive to missing data values. We introduce a new interaction data imputation method called network-guided matrix completion (NG-MC). The core part of NG-MC is low-rank probabilistic matrix completion that incorporates prior knowledge presented as a collection of gene networks. NG-MC assumes that interactions are transitive, such that latent gene interaction profiles inferred by NG-MC depend on the profiles of their direct neighbors in gene networks. As the NG-MC inference algorithm progresses, it propagates latent interaction profiles through each of the networks and updates gene network weights toward improved prediction. In a study with four different E-MAP data assays and considered protein–protein interaction and gene ontology similarity networks, NG-MC significantly surpassed existing alternative techniques. Inclusion of information from gene networks also allowed NG-MC to predict interactions for genes that were not included in original E-MAP assays, a task that could not be considered by current imputation approaches. PMID:25658751

Variations in Social Network Type Membership Among Older African Americans, Caribbean Blacks, and Non-Hispanic Whites

PubMed Central

2017-01-01

Abstract Objectives: This study examined race differences in the probability of belonging to a specific social network typology of family, friends, and church members. Method: Samples of African Americans, Caribbean blacks, and non-Hispanic whites aged 55+ were drawn from the National Survey of American Life. Typology indicators related to social integration and negative interactions with family, friendship, and church networks were used. Latent class analysis was used to identify typologies, and latent class multinomial logistic regression was used to assess the influence of race, and interactions between race and age, and race and education on typology membership. Results: Four network typologies were identified: optimal (high social integration, low negative interaction), family-centered (high social integration within primarily the extended family network, low negative interaction), strained (low social integration, high negative interaction), and ambivalent (high social integration and high negative interaction). Findings for race and age and race and education interactions indicated that the effects of education and age on typology membership varied by race. Discussion: Overall, the findings demonstrate how race interacts with age and education to influence the probability of belonging to particular network types. A better understanding of the influence of race, education, and age on social network typologies will inform future research and theoretical developments in this area. PMID:28329871

Probing Allosteric Inhibition Mechanisms of the Hsp70 Chaperone Proteins Using Molecular Dynamics Simulations and Analysis of the Residue Interaction Networks.

PubMed

Stetz, Gabrielle; Verkhivker, Gennady M

2016-08-22

Although molecular mechanisms of allosteric regulation in the Hsp70 chaperones have been extensively studied at both structural and functional levels, the current understanding of allosteric inhibition of chaperone activities by small molecules is still lacking. In the current study, using a battery of computational approaches, we probed allosteric inhibition mechanisms of E. coli Hsp70 (DnaK) and human Hsp70 proteins by small molecule inhibitors PET-16 and novolactone. Molecular dynamics simulations and binding free energy analysis were combined with network-based modeling of residue interactions and allosteric communications to systematically characterize and compare molecular signatures of the apo form, substrate-bound, and inhibitor-bound chaperone complexes. The results suggested a mechanism by which the allosteric inhibitors may leverage binding energy hotspots in the interaction networks to stabilize a specific conformational state and impair the interdomain allosteric control. Using the network-based centrality analysis and community detection, we demonstrated that substrate binding may strengthen the connectivity of local interaction communities, leading to a dense interaction network that can promote an efficient allosteric communication. In contrast, binding of PET-16 to DnaK may induce significant dynamic changes and lead to a fractured interaction network and impaired allosteric communications in the DnaK complex. By using a mechanistic-based analysis of distance fluctuation maps and allosteric propensities of protein residues, we determined that the allosteric network in the PET-16 complex may be small and localized due to the reduced communication and low cooperativity of the substrate binding loops, which may promote the higher rates of substrate dissociation and the decreased substrate affinity. In comparison with the significant effect of PET-16, binding of novolactone to HSPA1A may cause only moderate network changes and preserve allosteric coupling between the allosteric pocket and the substrate binding region. The impact of novolactone on the conformational dynamics and allosteric communications in the HSPA1A complex was comparable to the substrate effect, which is consistent with the experimental evidence that PET-16, but not novolactone binding, can significantly decrease substrate affinity. We argue that the unique dynamic and network signatures of PET-16 and novolactone may be linked with the experimentally observed functional effects of these inhibitors on allosteric regulation and substrate binding.

Interactivity vs. fairness in networked linux systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Wenji; Crawford, Matt; /Fermilab

In general, the Linux 2.6 scheduler can ensure fairness and provide excellent interactive performance at the same time. However, our experiments and mathematical analysis have shown that the current Linux interactivity mechanism tends to incorrectly categorize non-interactive network applications as interactive, which can lead to serious fairness or starvation issues. In the extreme, a single process can unjustifiably obtain up to 95% of the CPU! The root cause is due to the facts that: (1) network packets arrive at the receiver independently and discretely, and the 'relatively fast' non-interactive network process might frequently sleep to wait for packet arrival. Thoughmore » each sleep lasts for a very short period of time, the wait-for-packet sleeps occur so frequently that they lead to interactive status for the process. (2) The current Linux interactivity mechanism provides the possibility that a non-interactive network process could receive a high CPU share, and at the same time be incorrectly categorized as 'interactive.' In this paper, we propose and test a possible solution to address the interactivity vs. fairness problems. Experiment results have proved the effectiveness of the proposed solution.« less

Network Analysis Tools: from biological networks to clusters and pathways.

PubMed

Brohée, Sylvain; Faust, Karoline; Lima-Mendez, Gipsi; Vanderstocken, Gilles; van Helden, Jacques

2008-01-01

Network Analysis Tools (NeAT) is a suite of computer tools that integrate various algorithms for the analysis of biological networks: comparison between graphs, between clusters, or between graphs and clusters; network randomization; analysis of degree distribution; network-based clustering and path finding. The tools are interconnected to enable a stepwise analysis of the network through a complete analytical workflow. In this protocol, we present a typical case of utilization, where the tasks above are combined to decipher a protein-protein interaction network retrieved from the STRING database. The results returned by NeAT are typically subnetworks, networks enriched with additional information (i.e., clusters or paths) or tables displaying statistics. Typical networks comprising several thousands of nodes and arcs can be analyzed within a few minutes. The complete protocol can be read and executed in approximately 1 h.

A Global Protein Kinase and Phosphatase Interaction Network in Yeast

PubMed Central

Breitkreutz, Ashton; Choi, Hyungwon; Sharom, Jeffrey R.; Boucher, Lorrie; Neduva, Victor; Larsen, Brett; Lin, Zhen-Yuan; Breitkreutz, Bobby-Joe; Stark, Chris; Liu, Guomin; Ahn, Jessica; Dewar-Darch, Danielle; Reguly, Teresa; Tang, Xiaojing; Almeida, Ricardo; Qin, Zhaohui Steve; Pawson, Tony; Gingras, Anne-Claude; Nesvizhskii, Alexey I.; Tyers, Mike

2011-01-01

The interactions of protein kinases and phosphatases with their regulatory subunits and substrates underpin cellular regulation. We identified a kinase and phosphatase interaction (KPI) network of 1844 interactions in budding yeast by mass spectrometric analysis of protein complexes. The KPI network contained many dense local regions of interactions that suggested new functions. Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism, whereas interactions of the target of rapamycin complex 1 (TORC1) uncovered new effector kinases in nitrogen and carbon metabolism. An extensive backbone of kinase-kinase interactions cross-connects the proteome and may serve to coordinate diverse cellular responses. PMID:20489023

Using the principle of entropy maximization to infer genetic interaction networks from gene expression patterns.

PubMed

Lezon, Timothy R; Banavar, Jayanth R; Cieplak, Marek; Maritan, Amos; Fedoroff, Nina V

2006-12-12

We describe a method based on the principle of entropy maximization to identify the gene interaction network with the highest probability of giving rise to experimentally observed transcript profiles. In its simplest form, the method yields the pairwise gene interaction network, but it can also be extended to deduce higher-order interactions. Analysis of microarray data from genes in Saccharomyces cerevisiae chemostat cultures exhibiting energy metabolic oscillations identifies a gene interaction network that reflects the intracellular communication pathways that adjust cellular metabolic activity and cell division to the limiting nutrient conditions that trigger metabolic oscillations. The success of the present approach in extracting meaningful genetic connections suggests that the maximum entropy principle is a useful concept for understanding living systems, as it is for other complex, nonequilibrium systems.

Trauma-Exposed Latina Immigrants’ Networks: A Social Network Analysis Approach

PubMed Central

Hurtado-de-Mendoza, Alejandra; Serrano, Adriana; Gonzales, Felisa A.; Fernandez, Nicole C.; Cabling, Mark; Kaltman, Stacey

2015-01-01

Objective Trauma exposure among Latina immigrants is common. Social support networks can buffer the impact of trauma on mental health. This study characterizes the social networks of trauma-exposed Latina immigrants using a social network analysis perspective. Methods In 2011–2012 a convenience sample (n=28) of Latina immigrants with trauma exposure and presumptive depression or posttraumatic stress disorder was recruited from a community clinic in Washington DC. Participants completed a social network assessment and listed up to ten persons in their network (alters). E-Net was used to describe the aggregate structural, interactional, and functional characteristics of networks and Node-XL was used in a case study to diagram one network. Results Most participants listed children (93%), siblings (82%), and friends (71%) as alters, and most alters lived in the US (69%). Perceived emotional support and positive social interaction were higher compared to tangible, language, information, and financial support. A case study illustrates the use of network visualizations to assess the strengths and weaknesses of social networks. Conclusions Targeted social network interventions to enhance supportive networks among trauma-exposed Latina immigrants are warranted. PMID:28078194

Trauma-Exposed Latina Immigrants' Networks: A Social Network Analysis Approach.

PubMed

Hurtado-de-Mendoza, Alejandra; Serrano, Adriana; Gonzales, Felisa A; Fernandez, Nicole C; Cabling, Mark; Kaltman, Stacey

2016-11-01

Trauma exposure among Latina immigrants is common. Social support networks can buffer the impact of trauma on mental health. This study characterizes the social networks of trauma-exposed Latina immigrants using a social network analysis perspective. In 2011-2012 a convenience sample (n=28) of Latina immigrants with trauma exposure and presumptive depression or posttraumatic stress disorder was recruited from a community clinic in Washington DC. Participants completed a social network assessment and listed up to ten persons in their network (alters). E-Net was used to describe the aggregate structural, interactional, and functional characteristics of networks and Node-XL was used in a case study to diagram one network. Most participants listed children (93%), siblings (82%), and friends (71%) as alters, and most alters lived in the US (69%). Perceived emotional support and positive social interaction were higher compared to tangible, language, information, and financial support. A case study illustrates the use of network visualizations to assess the strengths and weaknesses of social networks. Targeted social network interventions to enhance supportive networks among trauma-exposed Latina immigrants are warranted.

Semantic integration to identify overlapping functional modules in protein interaction networks

PubMed Central

Cho, Young-Rae; Hwang, Woochang; Ramanathan, Murali; Zhang, Aidong

2007-01-01

Background The systematic analysis of protein-protein interactions can enable a better understanding of cellular organization, processes and functions. Functional modules can be identified from the protein interaction networks derived from experimental data sets. However, these analyses are challenging because of the presence of unreliable interactions and the complex connectivity of the network. The integration of protein-protein interactions with the data from other sources can be leveraged for improving the effectiveness of functional module detection algorithms. Results We have developed novel metrics, called semantic similarity and semantic interactivity, which use Gene Ontology (GO) annotations to measure the reliability of protein-protein interactions. The protein interaction networks can be converted into a weighted graph representation by assigning the reliability values to each interaction as a weight. We presented a flow-based modularization algorithm to efficiently identify overlapping modules in the weighted interaction networks. The experimental results show that the semantic similarity and semantic interactivity of interacting pairs were positively correlated with functional co-occurrence. The effectiveness of the algorithm for identifying modules was evaluated using functional categories from the MIPS database. We demonstrated that our algorithm had higher accuracy compared to other competing approaches. Conclusion The integration of protein interaction networks with GO annotation data and the capability of detecting overlapping modules substantially improve the accuracy of module identification. PMID:17650343

Default Network Modulation and Large-Scale Network Interactivity in Healthy Young and Old Adults

PubMed Central

Schacter, Daniel L.

2012-01-01

We investigated age-related changes in default, attention, and control network activity and their interactions in young and old adults. Brain activity during autobiographical and visuospatial planning was assessed using multivariate analysis and with intrinsic connectivity networks as regions of interest. In both groups, autobiographical planning engaged the default network while visuospatial planning engaged the attention network, consistent with a competition between the domains of internalized and externalized cognition. The control network was engaged for both planning tasks. In young subjects, the control network coupled with the default network during autobiographical planning and with the attention network during visuospatial planning. In old subjects, default-to-control network coupling was observed during both planning tasks, and old adults failed to deactivate the default network during visuospatial planning. This failure is not indicative of default network dysfunction per se, evidenced by default network engagement during autobiographical planning. Rather, a failure to modulate the default network in old adults is indicative of a lower degree of flexible network interactivity and reduced dynamic range of network modulation to changing task demands. PMID:22128194

Modelling the structure of a ceRNA-theoretical, bipartite microRNA-mRNA interaction network regulating intestinal epithelial cellular pathways using R programming.

PubMed

Robinson, J M; Henderson, W A

2018-01-12

We report a method using functional-molecular databases and network modelling to identify hypothetical mRNA-miRNA interaction networks regulating intestinal epithelial barrier function. The model forms a data-analysis component of our cell culture experiments, which produce RNA expression data from Nanostring Technologies nCounter ® system. The epithelial tight-junction (TJ) and actin cytoskeleton interact as molecular components of the intestinal epithelial barrier. Upstream regulation of TJ-cytoskeleton interaction is effected by the Rac/Rock/Rho signaling pathway and other associated pathways which may be activated or suppressed by extracellular signaling from growth factors, hormones, and immune receptors. Pathway activations affect epithelial homeostasis, contributing to degradation of the epithelial barrier associated with osmotic dysregulation, inflammation, and tumor development. The complexity underlying miRNA-mRNA interaction networks represents a roadblock for prediction and validation of competing-endogenous RNA network function. We developed a network model to identify hypothetical co-regulatory motifs in a miRNA-mRNA interaction network related to epithelial function. A mRNA-miRNA interaction list was generated using KEGG and miRWalk2.0 databases. R-code was developed to quantify and visualize inherent network structures. We identified a sub-network with a high number of shared, targeting miRNAs, of genes associated with cellular proliferation and cancer, including c-MYC and Cyclin D.

Pathway redundancy and protein essentiality revealed in the Saccharomyces cerevisiae interaction networks

PubMed Central

Ulitsky, Igor; Shamir, Ron

2007-01-01

The biological interpretation of genetic interactions is a major challenge. Recently, Kelley and Ideker proposed a method to analyze together genetic and physical networks, which explains many of the known genetic interactions as linking different pathways in the physical network. Here, we extend this method and devise novel analytic tools for interpreting genetic interactions in a physical context. Applying these tools on a large-scale Saccharomyces cerevisiae data set, our analysis reveals 140 between-pathway models that explain 3765 genetic interactions, roughly doubling those that were previously explained. Model genes tend to have short mRNA half-lives and many phosphorylation sites, suggesting that their stringent regulation is linked to pathway redundancy. We also identify ‘pivot' proteins that have many physical interactions with both pathways in our models, and show that pivots tend to be essential and highly conserved. Our analysis of models and pivots sheds light on the organization of the cellular machinery as well as on the roles of individual proteins. PMID:17437029

Modeling of intracerebral interictal epileptic discharges: Evidence for network interactions.

PubMed

Meesters, Stephan; Ossenblok, Pauly; Colon, Albert; Wagner, Louis; Schijns, Olaf; Boon, Paul; Florack, Luc; Fuster, Andrea

2018-06-01

The interictal epileptic discharges (IEDs) occurring in stereotactic EEG (SEEG) recordings are in general abundant compared to ictal discharges, but difficult to interpret due to complex underlying network interactions. A framework is developed to model these network interactions. To identify the synchronized neuronal activity underlying the IEDs, the variation in correlation over time of the SEEG signals is related to the occurrence of IEDs using the general linear model. The interdependency is assessed of the brain areas that reflect highly synchronized neural activity by applying independent component analysis, followed by cluster analysis of the spatial distributions of the independent components. The spatiotemporal interactions of the spike clusters reveal the leading or lagging of brain areas. The analysis framework was evaluated for five successfully operated patients, showing that the spike cluster that was related to the MRI-visible brain lesions coincided with the seizure onset zone. The additional value of the framework was demonstrated for two more patients, who were MRI-negative and for whom surgery was not successful. A network approach is promising in case of complex epilepsies. Analysis of IEDs is considered a valuable addition to routine review of SEEG recordings, with the potential to increase the success rate of epilepsy surgery. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

SpirPro: A Spirulina proteome database and web-based tools for the analysis of protein-protein interactions at the metabolic level in Spirulina (Arthrospira) platensis C1.

PubMed

Senachak, Jittisak; Cheevadhanarak, Supapon; Hongsthong, Apiradee

2015-07-29

Spirulina (Arthrospira) platensis is the only cyanobacterium that in addition to being studied at the molecular level and subjected to gene manipulation, can also be mass cultivated in outdoor ponds for commercial use as a food supplement. Thus, encountering environmental changes, including temperature stresses, is common during the mass production of Spirulina. The use of cyanobacteria as an experimental platform, especially for photosynthetic gene manipulation in plants and bacteria, is becoming increasingly important. Understanding the mechanisms and protein-protein interaction networks that underlie low- and high-temperature responses is relevant to Spirulina mass production. To accomplish this goal, high-throughput techniques such as OMICs analyses are used. Thus, large datasets must be collected, managed and subjected to information extraction. Therefore, databases including (i) proteomic analysis and protein-protein interaction (PPI) data and (ii) domain/motif visualization tools are required for potential use in temperature response models for plant chloroplasts and photosynthetic bacteria. A web-based repository was developed including an embedded database, SpirPro, and tools for network visualization. Proteome data were analyzed integrated with protein-protein interactions and/or metabolic pathways from KEGG. The repository provides various information, ranging from raw data (2D-gel images) to associated results, such as data from interaction and/or pathway analyses. This integration allows in silico analyses of protein-protein interactions affected at the metabolic level and, particularly, analyses of interactions between and within the affected metabolic pathways under temperature stresses for comparative proteomic analysis. The developed tool, which is coded in HTML with CSS/JavaScript and depicted in Scalable Vector Graphics (SVG), is designed for interactive analysis and exploration of the constructed network. SpirPro is publicly available on the web at http://spirpro.sbi.kmutt.ac.th . SpirPro is an analysis platform containing an integrated proteome and PPI database that provides the most comprehensive data on this cyanobacterium at the systematic level. As an integrated database, SpirPro can be applied in various analyses, such as temperature stress response networking analysis in cyanobacterial models and interacting domain-domain analysis between proteins of interest.

OmicsNet: a web-based tool for creation and visual analysis of biological networks in 3D space.

PubMed

Zhou, Guangyan; Xia, Jianguo

2018-06-07

Biological networks play increasingly important roles in omics data integration and systems biology. Over the past decade, many excellent tools have been developed to support creation, analysis and visualization of biological networks. However, important limitations remain: most tools are standalone programs, the majority of them focus on protein-protein interaction (PPI) or metabolic networks, and visualizations often suffer from 'hairball' effects when networks become large. To help address these limitations, we developed OmicsNet - a novel web-based tool that allows users to easily create different types of molecular interaction networks and visually explore them in a three-dimensional (3D) space. Users can upload one or multiple lists of molecules of interest (genes/proteins, microRNAs, transcription factors or metabolites) to create and merge different types of biological networks. The 3D network visualization system was implemented using the powerful Web Graphics Library (WebGL) technology that works natively in most major browsers. OmicsNet supports force-directed layout, multi-layered perspective layout, as well as spherical layout to help visualize and navigate complex networks. A rich set of functions have been implemented to allow users to perform coloring, shading, topology analysis, and enrichment analysis. OmicsNet is freely available at http://www.omicsnet.ca.

Interfacing cellular networks of S. cerevisiae and E. coli: Connecting dynamic and genetic information

PubMed Central

2013-01-01

Background In recent years, various types of cellular networks have penetrated biology and are nowadays used omnipresently for studying eukaryote and prokaryote organisms. Still, the relation and the biological overlap among phenomenological and inferential gene networks, e.g., between the protein interaction network and the gene regulatory network inferred from large-scale transcriptomic data, is largely unexplored. Results We provide in this study an in-depth analysis of the structural, functional and chromosomal relationship between a protein-protein network, a transcriptional regulatory network and an inferred gene regulatory network, for S. cerevisiae and E. coli. Further, we study global and local aspects of these networks and their biological information overlap by comparing, e.g., the functional co-occurrence of Gene Ontology terms by exploiting the available interaction structure among the genes. Conclusions Although the individual networks represent different levels of cellular interactions with global structural and functional dissimilarities, we observe crucial functions of their network interfaces for the assembly of protein complexes, proteolysis, transcription, translation, metabolic and regulatory interactions. Overall, our results shed light on the integrability of these networks and their interfacing biological processes. PMID:23663484

Cytoprophet: a Cytoscape plug-in for protein and domain interaction networks inference.

PubMed

Morcos, Faruck; Lamanna, Charles; Sikora, Marcin; Izaguirre, Jesús

2008-10-01

Cytoprophet is a software tool that allows prediction and visualization of protein and domain interaction networks. It is implemented as a plug-in of Cytoscape, an open source software framework for analysis and visualization of molecular networks. Cytoprophet implements three algorithms that predict new potential physical interactions using the domain composition of proteins and experimental assays. The algorithms for protein and domain interaction inference include maximum likelihood estimation (MLE) using expectation maximization (EM); the set cover approach maximum specificity set cover (MSSC) and the sum-product algorithm (SPA). After accepting an input set of proteins with Uniprot ID/Accession numbers and a selected prediction algorithm, Cytoprophet draws a network of potential interactions with probability scores and GO distances as edge attributes. A network of domain interactions between the domains of the initial protein list can also be generated. Cytoprophet was designed to take advantage of the visual capabilities of Cytoscape and be simple to use. An example of inference in a signaling network of myxobacterium Myxococcus xanthus is presented and available at Cytoprophet's website. http://cytoprophet.cse.nd.edu.

modPDZpep: a web resource for structure based analysis of human PDZ-mediated interaction networks.

PubMed

Sain, Neetu; Mohanty, Debasisa

2016-09-21

PDZ domains recognize short sequence stretches usually present in C-terminal of their interaction partners. Because of the involvement of PDZ domains in many important biological processes, several attempts have been made for developing bioinformatics tools for genome-wide identification of PDZ interaction networks. Currently available tools for prediction of interaction partners of PDZ domains utilize machine learning approach. Since, they have been trained using experimental substrate specificity data for specific PDZ families, their applicability is limited to PDZ families closely related to the training set. These tools also do not allow analysis of PDZ-peptide interaction interfaces. We have used a structure based approach to develop modPDZpep, a program to predict the interaction partners of human PDZ domains and analyze structural details of PDZ interaction interfaces. modPDZpep predicts interaction partners by using structural models of PDZ-peptide complexes and evaluating binding energy scores using residue based statistical pair potentials. Since, it does not require training using experimental data on peptide binding affinity, it can predict substrates for diverse PDZ families. Because of the use of simple scoring function for binding energy, it is also fast enough for genome scale structure based analysis of PDZ interaction networks. Benchmarking using artificial as well as real negative datasets indicates good predictive power with ROC-AUC values in the range of 0.7 to 0.9 for a large number of human PDZ domains. Another novel feature of modPDZpep is its ability to map novel PDZ mediated interactions in human protein-protein interaction networks, either by utilizing available experimental phage display data or by structure based predictions. In summary, we have developed modPDZpep, a web-server for structure based analysis of human PDZ domains. It is freely available at http://www.nii.ac.in/modPDZpep.html or http://202.54.226.235/modPDZpep.html . This article was reviewed by Michael Gromiha and Zoltán Gáspári.

Investigating Patterns of Interaction in Networked Learning and Computer-Supported Collaborative Learning: A Role for Social Network Analysis

ERIC Educational Resources Information Center

de Laat, Maarten; Lally, Vic; Lipponen, Lasse; Simons, Robert-Jan

2007-01-01

The focus of this study is to explore the advances that Social Network Analysis (SNA) can bring, in combination with other methods, when studying Networked Learning/Computer-Supported Collaborative Learning (NL/CSCL). We present a general overview of how SNA is applied in NL/CSCL research; we then go on to illustrate how this research method can…

System Analysis of LWDH Related Genes Based on Text Mining in Biological Networks

PubMed Central

Miao, Yingbo; Zhang, Liangcai; Wang, Yang; Feng, Rennan; Yang, Lei; Zhang, Shihua; Jiang, Yongshuai; Liu, Guiyou

2014-01-01

Liuwei-dihuang (LWDH) is widely used in traditional Chinese medicine (TCM), but its molecular mechanism about gene interactions is unclear. LWDH genes were extracted from the existing literatures based on text mining technology. To simulate the complex molecular interactions that occur in the whole body, protein-protein interaction networks (PPINs) were constructed and the topological properties of LWDH genes were analyzed. LWDH genes have higher centrality properties and may play important roles in the complex biological network environment. It was also found that the distances within LWDH genes are smaller than expected, which means that the communication of LWDH genes during the biological process is rapid and effectual. At last, a comprehensive network of LWDH genes, including the related drugs and regulatory pathways at both the transcriptional and posttranscriptional levels, was constructed and analyzed. The biological network analysis strategy used in this study may be helpful for the understanding of molecular mechanism of TCM. PMID:25243143

Interactions of the Salience Network and Its Subsystems with the Default-Mode and the Central-Executive Networks in Normal Aging and Mild Cognitive Impairment.

PubMed

Chand, Ganesh B; Wu, Junjie; Hajjar, Ihab; Qiu, Deqiang

2017-09-01

Previous functional magnetic resonance imaging (fMRI) investigations suggest that the intrinsically organized large-scale networks and the interaction between them might be crucial for cognitive activities. A triple network model, which consists of the default-mode network, salience network, and central-executive network, has been recently used to understand the connectivity patterns of the cognitively normal brains versus the brains with disorders. This model suggests that the salience network dynamically controls the default-mode and central-executive networks in healthy young individuals. However, the patterns of interactions have remained largely unknown in healthy aging or those with cognitive decline. In this study, we assess the patterns of interactions between the three networks using dynamical causal modeling in resting state fMRI data and compare them between subjects with normal cognition and mild cognitive impairment (MCI). In healthy elderly subjects, our analysis showed that the salience network, especially its dorsal subnetwork, modulates the interaction between the default-mode network and the central-executive network (Mann-Whitney U test; p < 0.05), which was consistent with the pattern of interaction reported in young adults. In contrast, this pattern of modulation by salience network was disrupted in MCI (p < 0.05). Furthermore, the degree of disruption in salience network control correlated significantly with lower overall cognitive performance measured by Montreal Cognitive Assessment (r = 0.295; p < 0.05). This study suggests that a disruption of the salience network control, especially the dorsal salience network, over other networks provides a neuronal basis for cognitive decline and may be a candidate neuroimaging biomarker of cognitive impairment.

An Analysis of Chemical Ingredients Network of Chinese Herbal Formulae for the Treatment of Coronary Heart Disease

PubMed Central

Ding, Fan; Zhang, Qianru; Ung, Carolina Oi Lam; Wang, Yitao; Han, Yifan; Hu, Yuanjia; Qi, Jin

2015-01-01

As a complex system, the complicated interactions between chemical ingredients, as well as the potential rules of interactive associations among chemical ingredients of traditional Chinese herbal formulae are not yet fully understood by modern science. On the other hand, network analysis is emerging as a powerful approach focusing on processing complex interactive data. By employing network approach in selected Chinese herbal formulae for the treatment of coronary heart disease (CHD), this article aims to construct and analyze chemical ingredients network of herbal formulae, and provide candidate herbs, chemical constituents, and ingredient groups for further investigation. As a result, chemical ingredients network composed of 1588 ingredients from 36 herbs used in 8 core formulae for the treatment of CHD was produced based on combination associations in herbal formulae. In this network, 9 communities with relative dense internal connections are significantly associated with 14 kinds of chemical structures with P<0.001. Moreover, chemical structural fingerprints of network communities were detected, while specific centralities of chemical ingredients indicating different levels of importance in the network were also measured. Finally, several distinct herbs, chemical ingredients, and ingredient groups with essential position in the network or high centrality value are recommended for further pharmacology study in the context of new drug development. PMID:25658855

Complexity of generic biochemical circuits: topology versus strength of interactions.

PubMed

Tikhonov, Mikhail; Bialek, William

2016-12-06

The historical focus on network topology as a determinant of biological function is still largely maintained today, illustrated by the rise of structure-only approaches to network analysis. However, biochemical circuits and genetic regulatory networks are defined both by their topology and by a multitude of continuously adjustable parameters, such as the strength of interactions between nodes, also recognized as important. Here we present a class of simple perceptron-based Boolean models within which comparing the relative importance of topology versus interaction strengths becomes a quantitatively well-posed problem. We quantify the intuition that for generic networks, optimization of interaction strengths is a crucial ingredient of achieving high complexity, defined here as the number of fixed points the network can accommodate. We propose a new methodology for characterizing the relative role of parameter optimization for topologies of a given class.

Timeline Resource Analysis Program (TRAP): User's manual and program document

NASA Technical Reports Server (NTRS)

Sessler, J. G.

1981-01-01

The Timeline Resource Analysis Program (TRAP), developed for scheduling and timelining problems, is described. Given an activity network, TRAP generates timeline plots, resource histograms, and tabular summaries of the network, schedules, and resource levels. It is written in ANSI FORTRAN for the Honeywell SIGMA 5 computer and operates in the interactive mode using the TEKTRONIX 4014-1 graphics terminal. The input network file may be a standard SIGMA 5 file or one generated using the Interactive Graphics Design System. The timeline plots can be displayed in two orderings: according to the sequence in which the tasks were read on input, and a waterfall sequence in which the tasks are ordered by start time. The input order is especially meaningful when the network consists of several interacting subnetworks. The waterfall sequence is helpful in assessing the project status at any point in time.

From brain to earth and climate systems: small-world interaction networks or not?

PubMed

Bialonski, Stephan; Horstmann, Marie-Therese; Lehnertz, Klaus

2010-03-01

We consider recent reports on small-world topologies of interaction networks derived from the dynamics of spatially extended systems that are investigated in diverse scientific fields such as neurosciences, geophysics, or meteorology. With numerical simulations that mimic typical experimental situations, we have identified an important constraint when characterizing such networks: indications of a small-world topology can be expected solely due to the spatial sampling of the system along with the commonly used time series analysis based approaches to network characterization.

Axelrod's Metanorm Games on Networks

PubMed Central

Galán, José M.; Łatek, Maciej M.; Rizi, Seyed M. Mussavi

2011-01-01

Metanorms is a mechanism proposed to promote cooperation in social dilemmas. Recent experimental results show that network structures that underlie social interactions influence the emergence of norms that promote cooperation. We generalize Axelrod's analysis of metanorms dynamics to interactions unfolding on networks through simulation and mathematical modeling. Network topology strongly influences the effectiveness of the metanorms mechanism in establishing cooperation. In particular, we find that average degree, clustering coefficient and the average number of triplets per node play key roles in sustaining or collapsing cooperation. PMID:21655211

Default and Executive Network Coupling Supports Creative Idea Production

PubMed Central

Beaty, Roger E.; Benedek, Mathias; Barry Kaufman, Scott; Silvia, Paul J.

2015-01-01

The role of attention in creative cognition remains controversial. Neuroimaging studies have reported activation of brain regions linked to both cognitive control and spontaneous imaginative processes, raising questions about how these regions interact to support creative thought. Using functional magnetic resonance imaging (fMRI), we explored this question by examining dynamic interactions between brain regions during a divergent thinking task. Multivariate pattern analysis revealed a distributed network associated with divergent thinking, including several core hubs of the default (posterior cingulate) and executive (dorsolateral prefrontal cortex) networks. The resting-state network affiliation of these regions was confirmed using data from an independent sample of participants. Graph theory analysis assessed global efficiency of the divergent thinking network, and network efficiency was found to increase as a function of individual differences in divergent thinking ability. Moreover, temporal connectivity analysis revealed increased coupling between default and salience network regions (bilateral insula) at the beginning of the task, followed by increased coupling between default and executive network regions at later stages. Such dynamic coupling suggests that divergent thinking involves cooperation between brain networks linked to cognitive control and spontaneous thought, which may reflect focused internal attention and the top-down control of spontaneous cognition during creative idea production. PMID:26084037

Timescale analysis of rule-based biochemical reaction networks

PubMed Central

Klinke, David J.; Finley, Stacey D.

2012-01-01

The flow of information within a cell is governed by a series of protein-protein interactions that can be described as a reaction network. Mathematical models of biochemical reaction networks can be constructed by repetitively applying specific rules that define how reactants interact and what new species are formed upon reaction. To aid in understanding the underlying biochemistry, timescale analysis is one method developed to prune the size of the reaction network. In this work, we extend the methods associated with timescale analysis to reaction rules instead of the species contained within the network. To illustrate this approach, we applied timescale analysis to a simple receptor-ligand binding model and a rule-based model of Interleukin-12 (IL-12) signaling in näive CD4+ T cells. The IL-12 signaling pathway includes multiple protein-protein interactions that collectively transmit information; however, the level of mechanistic detail sufficient to capture the observed dynamics has not been justified based upon the available data. The analysis correctly predicted that reactions associated with JAK2 and TYK2 binding to their corresponding receptor exist at a pseudo-equilibrium. In contrast, reactions associated with ligand binding and receptor turnover regulate cellular response to IL-12. An empirical Bayesian approach was used to estimate the uncertainty in the timescales. This approach complements existing rank- and flux-based methods that can be used to interrogate complex reaction networks. Ultimately, timescale analysis of rule-based models is a computational tool that can be used to reveal the biochemical steps that regulate signaling dynamics. PMID:21954150

NAP: The Network Analysis Profiler, a web tool for easier topological analysis and comparison of medium-scale biological networks.

PubMed

Theodosiou, Theodosios; Efstathiou, Georgios; Papanikolaou, Nikolas; Kyrpides, Nikos C; Bagos, Pantelis G; Iliopoulos, Ioannis; Pavlopoulos, Georgios A

2017-07-14

Nowadays, due to the technological advances of high-throughput techniques, Systems Biology has seen a tremendous growth of data generation. With network analysis, looking at biological systems at a higher level in order to better understand a system, its topology and the relationships between its components is of a great importance. Gene expression, signal transduction, protein/chemical interactions, biomedical literature co-occurrences, are few of the examples captured in biological network representations where nodes represent certain bioentities and edges represent the connections between them. Today, many tools for network visualization and analysis are available. Nevertheless, most of them are standalone applications that often (i) burden users with computing and calculation time depending on the network's size and (ii) focus on handling, editing and exploring a network interactively. While such functionality is of great importance, limited efforts have been made towards the comparison of the topological analysis of multiple networks. Network Analysis Provider (NAP) is a comprehensive web tool to automate network profiling and intra/inter-network topology comparison. It is designed to bridge the gap between network analysis, statistics, graph theory and partially visualization in a user-friendly way. It is freely available and aims to become a very appealing tool for the broader community. It hosts a great plethora of topological analysis methods such as node and edge rankings. Few of its powerful characteristics are: its ability to enable easy profile comparisons across multiple networks, find their intersection and provide users with simplified, high quality plots of any of the offered topological characteristics against any other within the same network. It is written in R and Shiny, it is based on the igraph library and it is able to handle medium-scale weighted/unweighted, directed/undirected and bipartite graphs. NAP is available at http://bioinformatics.med.uoc.gr/NAP .

Detection of protein complex from protein-protein interaction network using Markov clustering

NASA Astrophysics Data System (ADS)

Ochieng, P. J.; Kusuma, W. A.; Haryanto, T.

2017-05-01

Detection of complexes, or groups of functionally related proteins, is an important challenge while analysing biological networks. However, existing algorithms to identify protein complexes are insufficient when applied to dense networks of experimentally derived interaction data. Therefore, we introduced a graph clustering method based on Markov clustering algorithm to identify protein complex within highly interconnected protein-protein interaction networks. Protein-protein interaction network was first constructed to develop geometrical network, the network was then partitioned using Markov clustering to detect protein complexes. The interest of the proposed method was illustrated by its application to Human Proteins associated to type II diabetes mellitus. Flow simulation of MCL algorithm was initially performed and topological properties of the resultant network were analysed for detection of the protein complex. The results indicated the proposed method successfully detect an overall of 34 complexes with 11 complexes consisting of overlapping modules and 20 non-overlapping modules. The major complex consisted of 102 proteins and 521 interactions with cluster modularity and density of 0.745 and 0.101 respectively. The comparison analysis revealed MCL out perform AP, MCODE and SCPS algorithms with high clustering coefficient (0.751) network density and modularity index (0.630). This demonstrated MCL was the most reliable and efficient graph clustering algorithm for detection of protein complexes from PPI networks.

Genome-wide protein-protein interactions and protein function exploration in cyanobacteria

PubMed Central

Lv, Qi; Ma, Weimin; Liu, Hui; Li, Jiang; Wang, Huan; Lu, Fang; Zhao, Chen; Shi, Tieliu

2015-01-01

Genome-wide network analysis is well implemented to study proteins of unknown function. Here, we effectively explored protein functions and the biological mechanism based on inferred high confident protein-protein interaction (PPI) network in cyanobacteria. We integrated data from seven different sources and predicted 1,997 PPIs, which were evaluated by experiments in molecular mechanism, text mining of literatures in proved direct/indirect evidences, and “interologs” in conservation. Combined the predicted PPIs with known PPIs, we obtained 4,715 no-redundant PPIs (involving 3,231 proteins covering over 90% of genome) to generate the PPI network. Based on the PPI network, terms in Gene ontology (GO) were assigned to function-unknown proteins. Functional modules were identified by dissecting the PPI network into sub-networks and analyzing pathway enrichment, with which we investigated novel function of underlying proteins in protein complexes and pathways. Examples of photosynthesis and DNA repair indicate that the network approach is a powerful tool in protein function analysis. Overall, this systems biology approach provides a new insight into posterior functional analysis of PPIs in cyanobacteria. PMID:26490033

Social networks predict selective observation and information spread in ravens

PubMed Central

Rubenstein, Daniel I.; Bugnyar, Thomas; Hoppitt, William; Mikus, Nace; Schwab, Christine

2016-01-01

Animals are predicted to selectively observe and learn from the conspecifics with whom they share social connections. Yet, hardly anything is known about the role of different connections in observation and learning. To address the relationships between social connections, observation and learning, we investigated transmission of information in two raven (Corvus corax) groups. First, we quantified social connections in each group by constructing networks on affiliative interactions, aggressive interactions and proximity. We then seeded novel information by training one group member on a novel task and allowing others to observe. In each group, an observation network based on who observed whose task-solving behaviour was strongly correlated with networks based on affiliative interactions and proximity. Ravens with high social centrality (strength, eigenvector, information centrality) in the affiliative interaction network were also central in the observation network, possibly as a result of solving the task sooner. Network-based diffusion analysis revealed that the order that ravens first solved the task was best predicted by connections in the affiliative interaction network in a group of subadult ravens, and by social rank and kinship (which influenced affiliative interactions) in a group of juvenile ravens. Our results demonstrate that not all social connections are equally effective at predicting the patterns of selective observation and information transmission. PMID:27493780

Using the principle of entropy maximization to infer genetic interaction networks from gene expression patterns

PubMed Central

Lezon, Timothy R.; Banavar, Jayanth R.; Cieplak, Marek; Maritan, Amos; Fedoroff, Nina V.

2006-01-01

We describe a method based on the principle of entropy maximization to identify the gene interaction network with the highest probability of giving rise to experimentally observed transcript profiles. In its simplest form, the method yields the pairwise gene interaction network, but it can also be extended to deduce higher-order interactions. Analysis of microarray data from genes in Saccharomyces cerevisiae chemostat cultures exhibiting energy metabolic oscillations identifies a gene interaction network that reflects the intracellular communication pathways that adjust cellular metabolic activity and cell division to the limiting nutrient conditions that trigger metabolic oscillations. The success of the present approach in extracting meaningful genetic connections suggests that the maximum entropy principle is a useful concept for understanding living systems, as it is for other complex, nonequilibrium systems. PMID:17138668

Epidemic spread on interconnected metapopulation networks

NASA Astrophysics Data System (ADS)

Wang, Bing; Tanaka, Gouhei; Suzuki, Hideyuki; Aihara, Kazuyuki

2014-09-01

Numerous real-world networks have been observed to interact with each other, resulting in interconnected networks that exhibit diverse, nontrivial behavior with dynamical processes. Here we investigate epidemic spreading on interconnected networks at the level of metapopulation. Through a mean-field approximation for a metapopulation model, we find that both the interaction network topology and the mobility probabilities between subnetworks jointly influence the epidemic spread. Depending on the interaction between subnetworks, proper controls of mobility can efficiently mitigate epidemics, whereas an extremely biased mobility to one subnetwork will typically cause a severe outbreak and promote the epidemic spreading. Our analysis provides a basic framework for better understanding of epidemic behavior in related transportation systems as well as for better control of epidemics by guiding human mobility patterns.

Diversity of multilayer networks and its impact on collaborating epidemics

NASA Astrophysics Data System (ADS)

Min, Yong; Hu, Jiaren; Wang, Weihong; Ge, Ying; Chang, Jie; Jin, Xiaogang

2014-12-01

Interacting epidemics on diverse multilayer networks are increasingly important in modeling and analyzing the diffusion processes of real complex systems. A viral agent spreading on one layer of a multilayer network can interact with its counterparts by promoting (cooperative interaction), suppressing (competitive interaction), or inducing (collaborating interaction) its diffusion on other layers. Collaborating interaction displays different patterns: (i) random collaboration, where intralayer or interlayer induction has the same probability; (ii) concentrating collaboration, where consecutive intralayer induction is guaranteed with a probability of 1; and (iii) cascading collaboration, where consecutive intralayer induction is banned with a probability of 0. In this paper, we develop a top-bottom framework that uses only two distributions, the overlaid degree distribution and edge-type distribution, to model collaborating epidemics on multilayer networks. We then state the response of three collaborating patterns to structural diversity (evenness and difference of network layers). For viral agents with small transmissibility, we find that random collaboration is more effective in networks with higher diversity (high evenness and difference), while the concentrating pattern is more suitable in uneven networks. Interestingly, the cascading pattern requires a network with moderate difference and high evenness, and the moderately uneven coupling of multiple network layers can effectively increase robustness to resist cascading failure. With large transmissibility, however, we find that all collaborating patterns are more effective in high-diversity networks. Our work provides a systemic analysis of collaborating epidemics on multilayer networks. The results enhance our understanding of biotic and informative diffusion through multiple vectors.

Visualization of Metabolic Interaction Networks in Microbial Communities Using VisANT 5.0

PubMed Central

Wang, Yan; DeLisi, Charles; Segrè, Daniel; Hu, Zhenjun

2016-01-01

The complexity of metabolic networks in microbial communities poses an unresolved visualization and interpretation challenge. We address this challenge in the newly expanded version of a software tool for the analysis of biological networks, VisANT 5.0. We focus in particular on facilitating the visual exploration of metabolic interaction between microbes in a community, e.g. as predicted by COMETS (Computation of Microbial Ecosystems in Time and Space), a dynamic stoichiometric modeling framework. Using VisANT’s unique metagraph implementation, we show how one can use VisANT 5.0 to explore different time-dependent ecosystem-level metabolic networks. In particular, we analyze the metabolic interaction network between two bacteria previously shown to display an obligate cross-feeding interdependency. In addition, we illustrate how a putative minimal gut microbiome community could be represented in our framework, making it possible to highlight interactions across multiple coexisting species. We envisage that the “symbiotic layout” of VisANT can be employed as a general tool for the analysis of metabolism in complex microbial communities as well as heterogeneous human tissues. VisANT is freely available at: http://visant.bu.edu and COMETS at http://comets.bu.edu. PMID:27081850

Visualization of Metabolic Interaction Networks in Microbial Communities Using VisANT 5.0.

PubMed

Granger, Brian R; Chang, Yi-Chien; Wang, Yan; DeLisi, Charles; Segrè, Daniel; Hu, Zhenjun

2016-04-01

The complexity of metabolic networks in microbial communities poses an unresolved visualization and interpretation challenge. We address this challenge in the newly expanded version of a software tool for the analysis of biological networks, VisANT 5.0. We focus in particular on facilitating the visual exploration of metabolic interaction between microbes in a community, e.g. as predicted by COMETS (Computation of Microbial Ecosystems in Time and Space), a dynamic stoichiometric modeling framework. Using VisANT's unique metagraph implementation, we show how one can use VisANT 5.0 to explore different time-dependent ecosystem-level metabolic networks. In particular, we analyze the metabolic interaction network between two bacteria previously shown to display an obligate cross-feeding interdependency. In addition, we illustrate how a putative minimal gut microbiome community could be represented in our framework, making it possible to highlight interactions across multiple coexisting species. We envisage that the "symbiotic layout" of VisANT can be employed as a general tool for the analysis of metabolism in complex microbial communities as well as heterogeneous human tissues. VisANT is freely available at: http://visant.bu.edu and COMETS at http://comets.bu.edu.

Effective comparative analysis of protein-protein interaction networks by measuring the steady-state network flow using a Markov model.

PubMed

Jeong, Hyundoo; Qian, Xiaoning; Yoon, Byung-Jun

2016-10-06

Comparative analysis of protein-protein interaction (PPI) networks provides an effective means of detecting conserved functional network modules across different species. Such modules typically consist of orthologous proteins with conserved interactions, which can be exploited to computationally predict the modules through network comparison. In this work, we propose a novel probabilistic framework for comparing PPI networks and effectively predicting the correspondence between proteins, represented as network nodes, that belong to conserved functional modules across the given PPI networks. The basic idea is to estimate the steady-state network flow between nodes that belong to different PPI networks based on a Markov random walk model. The random walker is designed to make random moves to adjacent nodes within a PPI network as well as cross-network moves between potential orthologous nodes with high sequence similarity. Based on this Markov random walk model, we estimate the steady-state network flow - or the long-term relative frequency of the transitions that the random walker makes - between nodes in different PPI networks, which can be used as a probabilistic score measuring their potential correspondence. Subsequently, the estimated scores can be used for detecting orthologous proteins in conserved functional modules through network alignment. Through evaluations based on multiple real PPI networks, we demonstrate that the proposed scheme leads to improved alignment results that are biologically more meaningful at reduced computational cost, outperforming the current state-of-the-art algorithms. The source code and datasets can be downloaded from http://www.ece.tamu.edu/~bjyoon/CUFID .

Insights into the fold organization of TIM barrel from interaction energy based structure networks.

PubMed

Vijayabaskar, M S; Vishveshwara, Saraswathi

2012-01-01

There are many well-known examples of proteins with low sequence similarity, adopting the same structural fold. This aspect of sequence-structure relationship has been extensively studied both experimentally and theoretically, however with limited success. Most of the studies consider remote homology or "sequence conservation" as the basis for their understanding. Recently "interaction energy" based network formalism (Protein Energy Networks (PENs)) was developed to understand the determinants of protein structures. In this paper we have used these PENs to investigate the common non-covalent interactions and their collective features which stabilize the TIM barrel fold. We have also developed a method of aligning PENs in order to understand the spatial conservation of interactions in the fold. We have identified key common interactions responsible for the conservation of the TIM fold, despite high sequence dissimilarity. For instance, the central beta barrel of the TIM fold is stabilized by long-range high energy electrostatic interactions and low-energy contiguous vdW interactions in certain families. The other interfaces like the helix-sheet or the helix-helix seem to be devoid of any high energy conserved interactions. Conserved interactions in the loop regions around the catalytic site of the TIM fold have also been identified, pointing out their significance in both structural and functional evolution. Based on these investigations, we have developed a novel network based phylogenetic analysis for remote homologues, which can perform better than sequence based phylogeny. Such an analysis is more meaningful from both structural and functional evolutionary perspective. We believe that the information obtained through the "interaction conservation" viewpoint and the subsequently developed method of structure network alignment, can shed new light in the fields of fold organization and de novo computational protein design.

BIND: the Biomolecular Interaction Network Database

PubMed Central

Bader, Gary D.; Betel, Doron; Hogue, Christopher W. V.

2003-01-01

The Biomolecular Interaction Network Database (BIND: http://bind.ca) archives biomolecular interaction, complex and pathway information. A web-based system is available to query, view and submit records. BIND continues to grow with the addition of individual submissions as well as interaction data from the PDB and a number of large-scale interaction and complex mapping experiments using yeast two hybrid, mass spectrometry, genetic interactions and phage display. We have developed a new graphical analysis tool that provides users with a view of the domain composition of proteins in interaction and complex records to help relate functional domains to protein interactions. An interaction network clustering tool has also been developed to help focus on regions of interest. Continued input from users has helped further mature the BIND data specification, which now includes the ability to store detailed information about genetic interactions. The BIND data specification is available as ASN.1 and XML DTD. PMID:12519993

Interacting with Users in Social Networks: The Follow-back Problem

DTIC Science & Technology

2016-05-02

interacting with the friends of the target(s). Because forming a connection is known as following in social networks such as Twitter , we refer to this as...of an interaction resulting in a follow-back, we conduct an empirical analysis of several thousand interactions in Twitter . We build a model of the...define as the followback score. We show through simulation that these heuristic policies perform well on real Twitter graphs. Thesis Supervisor: Dr

Heterogeneity of interactions of microbial communities in regions of Taihu Lake with different nutrient loadings: A network analysis.

PubMed

Cao, Xinyi; Zhao, Dayong; Xu, Huimin; Huang, Rui; Zeng, Jin; Yu, Zhongbo

2018-06-11

To investigate the differences in the interactions of microbial communities in two regions in Taihu Lake with different nutrient loadings [Meiliang Bay (MLB) and Xukou Bay (XKB)], water samples were collected and both intra- and inter-kingdom microbial community interactions were examined with network analysis. It is demonstrated that all of the bacterioplankton, microeukaryotes and inter-kingdom communities networks in Taihu Lake were non-random. For the networks of bacterioplankton and inter-kingdom community in XKB, higher clustering coefficient and average degree but lower average path length indexes were observed, indicating the nodes in XKB were more clustered and closely connected with plenty edges than those of MLB. The bacterioplankton and inter-kingdom networks were considerably larger and more complex with more module hubs and connectors in XKB compared with those of MLB, whereas the microeukaryotes networks were comparable and had no module hubs or connectors in the two lake zones. The phyla of Acidobacteria, Cyanobacteria and Planctomycetes maintained greater cooperation with other phyla in XKB, rather than competition. The relationships between microbial communities and environmental factors in MLB were weaker. Compared with the microbial community networks of XKB, less modules in networks of MLB were significantly correlated with total phosphorous and total nitrogen.

Modular analysis of the probabilistic genetic interaction network.

PubMed

Hou, Lin; Wang, Lin; Qian, Minping; Li, Dong; Tang, Chao; Zhu, Yunping; Deng, Minghua; Li, Fangting

2011-03-15

Epistatic Miniarray Profiles (EMAP) has enabled the mapping of large-scale genetic interaction networks; however, the quantitative information gained from EMAP cannot be fully exploited since the data are usually interpreted as a discrete network based on an arbitrary hard threshold. To address such limitations, we adopted a mixture modeling procedure to construct a probabilistic genetic interaction network and then implemented a Bayesian approach to identify densely interacting modules in the probabilistic network. Mixture modeling has been demonstrated as an effective soft-threshold technique of EMAP measures. The Bayesian approach was applied to an EMAP dataset studying the early secretory pathway in Saccharomyces cerevisiae. Twenty-seven modules were identified, and 14 of those were enriched by gold standard functional gene sets. We also conducted a detailed comparison with state-of-the-art algorithms, hierarchical cluster and Markov clustering. The experimental results show that the Bayesian approach outperforms others in efficiently recovering biologically significant modules.

Machine Learning and Network Analysis of Molecular Dynamics Trajectories Reveal Two Chains of Red/Ox-specific Residue Interactions in Human Protein Disulfide Isomerase.

PubMed

Karamzadeh, Razieh; Karimi-Jafari, Mohammad Hossein; Sharifi-Zarchi, Ali; Chitsaz, Hamidreza; Salekdeh, Ghasem Hosseini; Moosavi-Movahedi, Ali Akbar

2017-06-16

The human protein disulfide isomerase (hPDI), is an essential four-domain multifunctional enzyme. As a result of disulfide shuffling in its terminal domains, hPDI exists in two oxidation states with different conformational preferences which are important for substrate binding and functional activities. Here, we address the redox-dependent conformational dynamics of hPDI through molecular dynamics (MD) simulations. Collective domain motions are identified by the principal component analysis of MD trajectories and redox-dependent opening-closing structure variations are highlighted on projected free energy landscapes. Then, important structural features that exhibit considerable differences in dynamics of redox states are extracted by statistical machine learning methods. Mapping the structural variations to time series of residue interaction networks also provides a holistic representation of the dynamical redox differences. With emphasizing on persistent long-lasting interactions, an approach is proposed that compiled these time series networks to a single dynamic residue interaction network (DRIN). Differential comparison of DRIN in oxidized and reduced states reveals chains of residue interactions that represent potential allosteric paths between catalytic and ligand binding sites of hPDI.

Discovering disease-associated genes in weighted protein-protein interaction networks

NASA Astrophysics Data System (ADS)

Cui, Ying; Cai, Meng; Stanley, H. Eugene

2018-04-01

Although there have been many network-based attempts to discover disease-associated genes, most of them have not taken edge weight - which quantifies their relative strength - into consideration. We use connection weights in a protein-protein interaction (PPI) network to locate disease-related genes. We analyze the topological properties of both weighted and unweighted PPI networks and design an improved random forest classifier to distinguish disease genes from non-disease genes. We use a cross-validation test to confirm that weighted networks are better able to discover disease-associated genes than unweighted networks, which indicates that including link weight in the analysis of network properties provides a better model of complex genotype-phenotype associations.

Changes in the interaction of resting-state neural networks from adolescence to adulthood.

PubMed

Stevens, Michael C; Pearlson, Godfrey D; Calhoun, Vince D

2009-08-01

This study examined how the mutual interactions of functionally integrated neural networks during resting-state fMRI differed between adolescence and adulthood. Independent component analysis (ICA) was used to identify functionally connected neural networks in 100 healthy participants aged 12-30 years. Hemodynamic timecourses that represented integrated neural network activity were analyzed with tools that quantified system "causal density" estimates, which indexed the proportion of significant Granger causality relationships among system nodes. Mutual influences among networks decreased with age, likely reflecting stronger within-network connectivity and more efficient between-network influences with greater development. Supplemental tests showed that this normative age-related reduction in causal density was accompanied by fewer significant connections to and from each network, regional increases in the strength of functional integration within networks, and age-related reductions in the strength of numerous specific system interactions. The latter included paths between lateral prefrontal-parietal circuits and "default mode" networks. These results contribute to an emerging understanding that activity in widely distributed networks thought to underlie complex cognition influences activity in other networks. (c) 2009 Wiley-Liss, Inc.

Alignment-free protein interaction network comparison

PubMed Central

Ali, Waqar; Rito, Tiago; Reinert, Gesine; Sun, Fengzhu; Deane, Charlotte M.

2014-01-01

Motivation: Biological network comparison software largely relies on the concept of alignment where close matches between the nodes of two or more networks are sought. These node matches are based on sequence similarity and/or interaction patterns. However, because of the incomplete and error-prone datasets currently available, such methods have had limited success. Moreover, the results of network alignment are in general not amenable for distance-based evolutionary analysis of sets of networks. In this article, we describe Netdis, a topology-based distance measure between networks, which offers the possibility of network phylogeny reconstruction. Results: We first demonstrate that Netdis is able to correctly separate different random graph model types independent of network size and density. The biological applicability of the method is then shown by its ability to build the correct phylogenetic tree of species based solely on the topology of current protein interaction networks. Our results provide new evidence that the topology of protein interaction networks contains information about evolutionary processes, despite the lack of conservation of individual interactions. As Netdis is applicable to all networks because of its speed and simplicity, we apply it to a large collection of biological and non-biological networks where it clusters diverse networks by type. Availability and implementation: The source code of the program is freely available at http://www.stats.ox.ac.uk/research/proteins/resources. Contact: w.ali@stats.ox.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25161230

Mapping biological process relationships and disease perturbations within a pathway network.

PubMed

Stoney, Ruth; Robertson, David L; Nenadic, Goran; Schwartz, Jean-Marc

2018-01-01

Molecular interaction networks are routinely used to map the organization of cellular function. Edges represent interactions between genes, proteins, or metabolites. However, in living cells, molecular interactions are dynamic, necessitating context-dependent models. Contextual information can be integrated into molecular interaction networks through the inclusion of additional molecular data, but there are concerns about completeness and relevance of this data. We developed an approach for representing the organization of human cellular processes using pathways as the nodes in a network. Pathways represent spatial and temporal sets of context-dependent interactions, generating a high-level network when linked together, which incorporates contextual information without the need for molecular interaction data. Analysis of the pathway network revealed linked communities representing functional relationships, comparable to those found in molecular networks, including metabolism, signaling, immunity, and the cell cycle. We mapped a range of diseases onto this network and find that pathways associated with diseases tend to be functionally connected, highlighting the perturbed functions that result in disease phenotypes. We demonstrated that disease pathways cluster within the network. We then examined the distribution of cancer pathways and showed that cancer pathways tend to localize within the signaling, DNA processes and immune modules, although some cancer-associated nodes are found in other network regions. Altogether, we generated a high-confidence functional network, which avoids some of the shortcomings faced by conventional molecular models. Our representation provides an intuitive functional interpretation of cellular organization, which relies only on high-quality pathway and Gene Ontology data. The network is available at https://data.mendeley.com/datasets/3pbwkxjxg9/1.

Identification of GRB2 and GAB1 Coexpression as an Unfavorable Prognostic Factor for Hepatocellular Carcinoma by a Combination of Expression Profile and Network Analysis

PubMed Central

Yang, Mei; Wang, Danhua; Yu, Lingxiang; Guo, Chaonan; Guo, Xiaodong; Lin, Na

2013-01-01

Aim To screen novel markers for hepatocellular carcinoma (HCC) by a combination of expression profile, interaction network analysis and clinical validation. Methods HCC significant molecules which are differentially expressed or had genetic variations in HCC tissues were obtained from five existing HCC related databases (OncoDB.HCC, HCC.net, dbHCCvar, EHCO and Liverome). Then, the protein-protein interaction (PPI) network of these molecules was constructed. Three topological features of the network ('Degree', 'Betweenness', and 'Closeness') and the k-core algorithm were used to screen candidate HCC markers which play crucial roles in tumorigenesis of HCC. Furthermore, the clinical significance of two candidate HCC markers growth factor receptor-bound 2 (GRB2) and GRB2-associated-binding protein 1 (GAB1) was validated. Results In total, 6179 HCC significant genes and 977 HCC significant proteins were collected from existing HCC related databases. After network analysis, 331 candidate HCC markers were identified. Especially, GAB1 has the highest k-coreness suggesting its central localization in HCC related network, and the interaction between GRB2 and GAB1 has the largest edge-betweenness implying it may be biologically important to the function of HCC related network. As the results of clinical validation, the expression levels of both GRB2 and GAB1 proteins were significantly higher in HCC tissues than those in their adjacent nonneoplastic tissues. More importantly, the combined GRB2 and GAB1 protein expression was significantly associated with aggressive tumor progression and poor prognosis in patients with HCC. Conclusion This study provided an integrative analysis by combining expression profile and interaction network analysis to identify a list of biologically significant HCC related markers and pathways. Further experimental validation indicated that the aberrant expression of GRB2 and GAB1 proteins may be strongly related to tumor progression and prognosis in patients with HCC. The overexpression of GRB2 in combination with upregulation of GAB1 may be an unfavorable prognostic factor for HCC. PMID:24391994

Integrating epigenomic data and 3D genomic structure with a new measure of chromatin assortativity.

PubMed

Pancaldi, Vera; Carrillo-de-Santa-Pau, Enrique; Javierre, Biola Maria; Juan, David; Fraser, Peter; Spivakov, Mikhail; Valencia, Alfonso; Rico, Daniel

2016-07-08

Network analysis is a powerful way of modeling chromatin interactions. Assortativity is a network property used in social sciences to identify factors affecting how people establish social ties. We propose a new approach, using chromatin assortativity, to integrate the epigenomic landscape of a specific cell type with its chromatin interaction network and thus investigate which proteins or chromatin marks mediate genomic contacts. We use high-resolution promoter capture Hi-C and Hi-Cap data as well as ChIA-PET data from mouse embryonic stem cells to investigate promoter-centered chromatin interaction networks and calculate the presence of specific epigenomic features in the chromatin fragments constituting the nodes of the network. We estimate the association of these features with the topology of four chromatin interaction networks and identify features localized in connected areas of the network. Polycomb group proteins and associated histone marks are the features with the highest chromatin assortativity in promoter-centered networks. We then ask which features distinguish contacts amongst promoters from contacts between promoters and other genomic elements. We observe higher chromatin assortativity of the actively elongating form of RNA polymerase 2 (RNAPII) compared with inactive forms only in interactions between promoters and other elements. Contacts among promoters and between promoters and other elements have different characteristic epigenomic features. We identify a possible role for the elongating form of RNAPII in mediating interactions among promoters, enhancers, and transcribed gene bodies. Our approach facilitates the study of multiple genome-wide epigenomic profiles, considering network topology and allowing the comparison of chromatin interaction networks.

Topological, functional, and dynamic properties of the protein interaction networks rewired by benzo(a)pyrene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ba, Qian; Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing; Li, Junyang

2015-03-01

Benzo(a)pyrene is a common environmental and foodborne pollutant that has been identified as a human carcinogen. Although the carcinogenicity of benzo(a)pyrene has been extensively reported, its precise molecular mechanisms and the influence on system-level protein networks are not well understood. To investigate the system-level influence of benzo(a)pyrene on protein interactions and regulatory networks, a benzo(a)pyrene-rewired protein interaction network was constructed based on 769 key proteins derived from more than 500 literature reports. The protein interaction network rewired by benzo(a)pyrene was a scale-free, highly-connected biological system. Ten modules were identified, and 25 signaling pathways were enriched, most of which belong tomore » the human diseases category, especially cancer and infectious disease. In addition, two lung-specific and two liver-specific pathways were identified. Three pathways were specific in short and medium-term networks (< 48 h), and five pathways were enriched only in the medium-term network (6 h–48 h). Finally, the expression of linker genes in the network was validated by Western blotting. These findings establish the overall, tissue- and time-specific benzo(a)pyrene-rewired protein interaction networks and provide insights into the biological effects and molecular mechanisms of action of benzo(a)pyrene. - Highlights: • Benzo(a)pyrene induced scale-free, highly-connected protein interaction networks. • 25 signaling pathways were enriched through modular analysis. • Tissue- and time-specific pathways were identified.« less

Visualization of metabolic interaction networks in microbial communities using VisANT 5.0

DOE PAGES

Granger, Brian R.; Chang, Yi -Chien; Wang, Yan; ...

2016-04-15

Here, the complexity of metabolic networks in microbial communities poses an unresolved visualization and interpretation challenge. We address this challenge in the newly expanded version of a software tool for the analysis of biological networks, VisANT 5.0. We focus in particular on facilitating the visual exploration of metabolic interaction between microbes in a community, e.g. as predicted by COMETS (Computation of Microbial Ecosystems in Time and Space), a dynamic stoichiometric modeling framework. Using VisANT's unique meta-graph implementation, we show how one can use VisANT 5.0 to explore different time-dependent ecosystem-level metabolic networks. In particular, we analyze the metabolic interaction networkmore » between two bacteria previously shown to display an obligate cross-feeding interdependency. In addition, we illustrate how a putative minimal gut microbiome community could be represented in our framework, making it possible to highlight interactions across multiple coexisting species. We envisage that the "symbiotic layout" of VisANT can be employed as a general tool for the analysis of metabolism in complex microbial communities as well as heterogeneous human tissues.« less

GIANT 2.0: genome-scale integrated analysis of gene networks in tissues.

PubMed

Wong, Aaron K; Krishnan, Arjun; Troyanskaya, Olga G

2018-05-25

GIANT2 (Genome-wide Integrated Analysis of gene Networks in Tissues) is an interactive web server that enables biomedical researchers to analyze their proteins and pathways of interest and generate hypotheses in the context of genome-scale functional maps of human tissues. The precise actions of genes are frequently dependent on their tissue context, yet direct assay of tissue-specific protein function and interactions remains infeasible in many normal human tissues and cell-types. With GIANT2, researchers can explore predicted tissue-specific functional roles of genes and reveal changes in those roles across tissues, all through interactive multi-network visualizations and analyses. Additionally, the NetWAS approach available through the server uses tissue-specific/cell-type networks predicted by GIANT2 to re-prioritize statistical associations from GWAS studies and identify disease-associated genes. GIANT2 predicts tissue-specific interactions by integrating diverse functional genomics data from now over 61 400 experiments for 283 diverse tissues and cell-types. GIANT2 does not require any registration or installation and is freely available for use at http://giant-v2.princeton.edu.

Network Analysis of Drug-target Interactions: A Study on FDA-approved New Molecular Entities Between 2000 to 2015.

PubMed

Lin, Hui-Heng; Zhang, Le-Le; Yan, Ru; Lu, Jin-Jian; Hu, Yuanjia

2017-09-25

The U.S. Food and Drug Administration (FDA) approves new drugs every year. Drug targets are some of the most important interactive molecules for drugs, as they have a significant impact on the therapeutic effects of drugs. In this work, we thoroughly analyzed the data of small molecule drugs approved by the U.S. FDA between 2000 and 2015. Specifically, we focused on seven classes of new molecular entity (NME) classified by the anatomic therapeutic chemical (ATC) classification system. They were NMEs and their corresponding targets for the cardiovascular system, respiratory system, nerve system, general anti-infective systemic, genito-urinary system and sex hormones, alimentary tract and metabolisms, and antineoplastic and immunomodulating agents. To study the drug-target interaction on the systems level, we employed network topological analysis and multipartite network projections. As a result, the drug-target relations of different kinds of drugs were comprehensively characterized and global pictures of drug-target, drug-drug, and target-target interactions were visualized and analyzed from the perspective of network models.

Large-scale De Novo Prediction of Physical Protein-Protein Association*

PubMed Central

Elefsinioti, Antigoni; Saraç, Ömer Sinan; Hegele, Anna; Plake, Conrad; Hubner, Nina C.; Poser, Ina; Sarov, Mihail; Hyman, Anthony; Mann, Matthias; Schroeder, Michael; Stelzl, Ulrich; Beyer, Andreas

2011-01-01

Information about the physical association of proteins is extensively used for studying cellular processes and disease mechanisms. However, complete experimental mapping of the human interactome will remain prohibitively difficult in the near future. Here we present a map of predicted human protein interactions that distinguishes functional association from physical binding. Our network classifies more than 5 million protein pairs predicting 94,009 new interactions with high confidence. We experimentally tested a subset of these predictions using yeast two-hybrid analysis and affinity purification followed by quantitative mass spectrometry. Thus we identified 462 new protein-protein interactions and confirmed the predictive power of the network. These independent experiments address potential issues of circular reasoning and are a distinctive feature of this work. Analysis of the physical interactome unravels subnetworks mediating between different functional and physical subunits of the cell. Finally, we demonstrate the utility of the network for the analysis of molecular mechanisms of complex diseases by applying it to genome-wide association studies of neurodegenerative diseases. This analysis provides new evidence implying TOMM40 as a factor involved in Alzheimer's disease. The network provides a high-quality resource for the analysis of genomic data sets and genetic association studies in particular. Our interactome is available via the hPRINT web server at: www.print-db.org. PMID:21836163

Evaluating multiple determinants of the structure of plant-animal mutualistic networks.

PubMed

Vázquez, Diego P; Chacoff, Natacha P; Cagnolo, Luciano

2009-08-01

The structure of mutualistic networks is likely to result from the simultaneous influence of neutrality and the constraints imposed by complementarity in species phenotypes, phenologies, spatial distributions, phylogenetic relationships, and sampling artifacts. We develop a conceptual and methodological framework to evaluate the relative contributions of these potential determinants. Applying this approach to the analysis of a plant-pollinator network, we show that information on relative abundance and phenology suffices to predict several aggregate network properties (connectance, nestedness, interaction evenness, and interaction asymmetry). However, such information falls short of predicting the detailed network structure (the frequency of pairwise interactions), leaving a large amount of variation unexplained. Taken together, our results suggest that both relative species abundance and complementarity in spatiotemporal distribution contribute substantially to generate observed network patters, but that this information is by no means sufficient to predict the occurrence and frequency of pairwise interactions. Future studies could use our methodological framework to evaluate the generality of our findings in a representative sample of study systems with contrasting ecological conditions.

Revealing gene regulation and association through biological networks

USDA-ARS?s Scientific Manuscript database

This review had first summarized traditional methods used by plant breeders for genetic improvement, such as QTL analysis and transcriptomic analysis. With accumulating data, we can draw a network that comprises all possible links between members of a community, including protein–protein interaction...

Ecological network analysis on global virtual water trade.

PubMed

Yang, Zhifeng; Mao, Xufeng; Zhao, Xu; Chen, Bin

2012-02-07

Global water interdependencies are likely to increase with growing virtual water trade. To address the issues of the indirect effects of water trade through the global economic circulation, we use ecological network analysis (ENA) to shed insight into the complicated system interactions. A global model of virtual water flow among agriculture and livestock production trade in 1995-1999 is also built as the basis for network analysis. Control analysis is used to identify the quantitative control or dependency relations. The utility analysis provides more indicators for describing the mutual relationship between two regions/countries by imitating the interactions in the ecosystem and distinguishes the beneficiary and the contributor of virtual water trade system. Results show control and utility relations can well depict the mutual relation in trade system, and direct observable relations differ from integral ones with indirect interactions considered. This paper offers a new way to depict the interrelations between trade components and can serve as a meaningful start as we continue to use ENA in providing more valuable implications for freshwater study on a global scale.

Synchronization unveils the organization of ecological networks with positive and negative interactions

NASA Astrophysics Data System (ADS)

Girón, Andrea; Saiz, Hugo; Bacelar, Flora S.; Andrade, Roberto F. S.; Gómez-Gardeñes, Jesús

2016-06-01

Network science has helped to understand the organization principles of the interactions among the constituents of large complex systems. However, recently, the high resolution of the data sets collected has allowed to capture the different types of interactions coexisting within the same system. A particularly important example is that of systems with positive and negative interactions, a usual feature appearing in social, neural, and ecological systems. The interplay of links of opposite sign presents natural difficulties for generalizing typical concepts and tools applied to unsigned networks and, moreover, poses some questions intrinsic to the signed nature of the network, such as how are negative interactions balanced by positive ones so to allow the coexistence and survival of competitors/foes within the same system? Here, we show that synchronization phenomenon is an ideal benchmark for uncovering such balance and, as a byproduct, to assess which nodes play a critical role in the overall organization of the system. We illustrate our findings with the analysis of synthetic and real ecological networks in which facilitation and competitive interactions coexist.

An ultrastructural analysis of platelets, erythrocytes, white blood cells, and fibrin network in systemic lupus erythematosus.

PubMed

Pretorius, Etheresia; du Plooy, Jenny; Soma, Prashilla; Gasparyan, Armen Yuri

2014-07-01

The study suggests that patients with systemic lupus erythematosus (SLE) present with distinct inflammatory ultrastructural changes such as platelets blebbing, generation of platelet-derived microparticles, spontaneous formation of massive fibrin network and fusion of the erythrocytes membranes. Lupoid platelets actively interact with other inflammatory cells, particularly with white blood cells (WBCs), and the massive fibrin network facilitates such an interaction. It is possible that the concerted actions of platelets, erythrocytes and WBC, caught in the inflammatory fibrin network, predispose to pro-thrombotic states in patients with SLE.

Unraveling spurious properties of interaction networks with tailored random networks.

PubMed

Bialonski, Stephan; Wendler, Martin; Lehnertz, Klaus

2011-01-01

We investigate interaction networks that we derive from multivariate time series with methods frequently employed in diverse scientific fields such as biology, quantitative finance, physics, earth and climate sciences, and the neurosciences. Mimicking experimental situations, we generate time series with finite length and varying frequency content but from independent stochastic processes. Using the correlation coefficient and the maximum cross-correlation, we estimate interdependencies between these time series. With clustering coefficient and average shortest path length, we observe unweighted interaction networks, derived via thresholding the values of interdependence, to possess non-trivial topologies as compared to Erdös-Rényi networks, which would indicate small-world characteristics. These topologies reflect the mostly unavoidable finiteness of the data, which limits the reliability of typically used estimators of signal interdependence. We propose random networks that are tailored to the way interaction networks are derived from empirical data. Through an exemplary investigation of multichannel electroencephalographic recordings of epileptic seizures--known for their complex spatial and temporal dynamics--we show that such random networks help to distinguish network properties of interdependence structures related to seizure dynamics from those spuriously induced by the applied methods of analysis.

Unraveling Spurious Properties of Interaction Networks with Tailored Random Networks

PubMed Central

Bialonski, Stephan; Wendler, Martin; Lehnertz, Klaus

2011-01-01

We investigate interaction networks that we derive from multivariate time series with methods frequently employed in diverse scientific fields such as biology, quantitative finance, physics, earth and climate sciences, and the neurosciences. Mimicking experimental situations, we generate time series with finite length and varying frequency content but from independent stochastic processes. Using the correlation coefficient and the maximum cross-correlation, we estimate interdependencies between these time series. With clustering coefficient and average shortest path length, we observe unweighted interaction networks, derived via thresholding the values of interdependence, to possess non-trivial topologies as compared to Erdös-Rényi networks, which would indicate small-world characteristics. These topologies reflect the mostly unavoidable finiteness of the data, which limits the reliability of typically used estimators of signal interdependence. We propose random networks that are tailored to the way interaction networks are derived from empirical data. Through an exemplary investigation of multichannel electroencephalographic recordings of epileptic seizures – known for their complex spatial and temporal dynamics – we show that such random networks help to distinguish network properties of interdependence structures related to seizure dynamics from those spuriously induced by the applied methods of analysis. PMID:21850239

Wavelet and Multiresolution Analysis for Finite Element Networking Paradigms

NASA Technical Reports Server (NTRS)

Kurdila, Andrew J.; Sharpley, Robert C.

1999-01-01

This paper presents a final report on Wavelet and Multiresolution Analysis for Finite Element Networking Paradigms. The focus of this research is to derive and implement: 1) Wavelet based methodologies for the compression, transmission, decoding, and visualization of three dimensional finite element geometry and simulation data in a network environment; 2) methodologies for interactive algorithm monitoring and tracking in computational mechanics; and 3) Methodologies for interactive algorithm steering for the acceleration of large scale finite element simulations. Also included in this report are appendices describing the derivation of wavelet based Particle Image Velocity algorithms and reduced order input-output models for nonlinear systems by utilizing wavelet approximations.

Assessing Group Interaction with Social Language Network Analysis

NASA Astrophysics Data System (ADS)

Scholand, Andrew J.; Tausczik, Yla R.; Pennebaker, James W.

In this paper we discuss a new methodology, social language network analysis (SLNA), that combines tools from social language processing and network analysis to assess socially situated working relationships within a group. Specifically, SLNA aims to identify and characterize the nature of working relationships by processing artifacts generated with computer-mediated communication systems, such as instant message texts or emails. Because social language processing is able to identify psychological, social, and emotional processes that individuals are not able to fully mask, social language network analysis can clarify and highlight complex interdependencies between group members, even when these relationships are latent or unrecognized.

Social Network Behavior and Engagement Within a Smoking Cessation Facebook Page

PubMed Central

Cole-Lewis, Heather; Perotte, Adler; Galica, Kasia; Dreyer, Lindy; Griffith, Christopher; Schwarz, Mary; Yun, Christopher; Patrick, Heather; Coa, Kisha

2016-01-01

Background Social media platforms are increasingly being used to support individuals in behavior change attempts, including smoking cessation. Examining the interactions of participants in health-related social media groups can help inform our understanding of how these groups can best be leveraged to facilitate behavior change. Objective The aim of this study was to analyze patterns of participation, self-reported smoking cessation length, and interactions within the National Cancer Institutes’ Facebook community for smoking cessation support. Methods Our sample consisted of approximately 4243 individuals who interacted (eg, posted, commented) on the public Smokefree Women Facebook page during the time of data collection. In Phase 1, social network visualizations and centrality measures were used to evaluate network structure and engagement. In Phase 2, an inductive, thematic qualitative content analysis was conducted with a subsample of 500 individuals, and correlational analysis was used to determine how participant engagement was associated with self-reported session length. Results Between February 2013 and March 2014, there were 875 posts and 4088 comments from approximately 4243 participants. Social network visualizations revealed the moderator’s role in keeping the community together and distributing the most active participants. Correlation analyses suggest that engagement in the network was significantly inversely associated with cessation status (Spearman correlation coefficient = −0.14, P=.03, N=243). The content analysis of 1698 posts from 500 randomly selected participants identified the most frequent interactions in the community as providing support (43%, n=721) and announcing number of days smoke free (41%, n=689). Conclusions These findings highlight the importance of the moderator for network engagement and provide helpful insights into the patterns and types of interactions participants are engaging in. This study adds knowledge of how the social network of a smoking cessation community behaves within the confines of a Facebook group. PMID:27485315

Visual analysis and exploration of complex corporate shareholder networks

NASA Astrophysics Data System (ADS)

Tekušová, Tatiana; Kohlhammer, Jörn

2008-01-01

The analysis of large corporate shareholder network structures is an important task in corporate governance, in financing, and in financial investment domains. In a modern economy, large structures of cross-corporation, cross-border shareholder relationships exist, forming complex networks. These networks are often difficult to analyze with traditional approaches. An efficient visualization of the networks helps to reveal the interdependent shareholding formations and the controlling patterns. In this paper, we propose an effective visualization tool that supports the financial analyst in understanding complex shareholding networks. We develop an interactive visual analysis system by combining state-of-the-art visualization technologies with economic analysis methods. Our system is capable to reveal patterns in large corporate shareholder networks, allows the visual identification of the ultimate shareholders, and supports the visual analysis of integrated cash flow and control rights. We apply our system on an extensive real-world database of shareholder relationships, showing its usefulness for effective visual analysis.

miRNet - dissecting miRNA-target interactions and functional associations through network-based visual analysis

PubMed Central

Fan, Yannan; Siklenka, Keith; Arora, Simran K.; Ribeiro, Paula; Kimmins, Sarah; Xia, Jianguo

2016-01-01

MicroRNAs (miRNAs) can regulate nearly all biological processes and their dysregulation is implicated in various complex diseases and pathological conditions. Recent years have seen a growing number of functional studies of miRNAs using high-throughput experimental technologies, which have produced a large amount of high-quality data regarding miRNA target genes and their interactions with small molecules, long non-coding RNAs, epigenetic modifiers, disease associations, etc. These rich sets of information have enabled the creation of comprehensive networks linking miRNAs with various biologically important entities to shed light on their collective functions and regulatory mechanisms. Here, we introduce miRNet, an easy-to-use web-based tool that offers statistical, visual and network-based approaches to help researchers understand miRNAs functions and regulatory mechanisms. The key features of miRNet include: (i) a comprehensive knowledge base integrating high-quality miRNA-target interaction data from 11 databases; (ii) support for differential expression analysis of data from microarray, RNA-seq and quantitative PCR; (iii) implementation of a flexible interface for data filtering, refinement and customization during network creation; (iv) a powerful fully featured network visualization system coupled with enrichment analysis. miRNet offers a comprehensive tool suite to enable statistical analysis and functional interpretation of various data generated from current miRNA studies. miRNet is freely available at http://www.mirnet.ca. PMID:27105848

Dynamic Processes in Network Goods: Modeling, Analysis and Applications

ERIC Educational Resources Information Center

Paothong, Arnut

2013-01-01

The network externality function plays a very important role in the study of economic network industries. Moreover, the consumer group dynamic interactions coupled with network externality concept is going to play a dominant role in the network goods in the 21st century. The existing literature is stemmed on a choice of externality function with…

QuIN: A Web Server for Querying and Visualizing Chromatin Interaction Networks.

PubMed

Thibodeau, Asa; Márquez, Eladio J; Luo, Oscar; Ruan, Yijun; Menghi, Francesca; Shin, Dong-Guk; Stitzel, Michael L; Vera-Licona, Paola; Ucar, Duygu

2016-06-01

Recent studies of the human genome have indicated that regulatory elements (e.g. promoters and enhancers) at distal genomic locations can interact with each other via chromatin folding and affect gene expression levels. Genomic technologies for mapping interactions between DNA regions, e.g., ChIA-PET and HiC, can generate genome-wide maps of interactions between regulatory elements. These interaction datasets are important resources to infer distal gene targets of non-coding regulatory elements and to facilitate prioritization of critical loci for important cellular functions. With the increasing diversity and complexity of genomic information and public ontologies, making sense of these datasets demands integrative and easy-to-use software tools. Moreover, network representation of chromatin interaction maps enables effective data visualization, integration, and mining. Currently, there is no software that can take full advantage of network theory approaches for the analysis of chromatin interaction datasets. To fill this gap, we developed a web-based application, QuIN, which enables: 1) building and visualizing chromatin interaction networks, 2) annotating networks with user-provided private and publicly available functional genomics and interaction datasets, 3) querying network components based on gene name or chromosome location, and 4) utilizing network based measures to identify and prioritize critical regulatory targets and their direct and indirect interactions. QuIN's web server is available at http://quin.jax.org QuIN is developed in Java and JavaScript, utilizing an Apache Tomcat web server and MySQL database and the source code is available under the GPLV3 license available on GitHub: https://github.com/UcarLab/QuIN/.

The Knowledge-Integrated Network Biomarkers Discovery for Major Adverse Cardiac Events

PubMed Central

Jin, Guangxu; Zhou, Xiaobo; Wang, Honghui; Zhao, Hong; Cui, Kemi; Zhang, Xiang-Sun; Chen, Luonan; Hazen, Stanley L.; Li, King; Wong, Stephen T. C.

2010-01-01

The mass spectrometry (MS) technology in clinical proteomics is very promising for discovery of new biomarkers for diseases management. To overcome the obstacles of data noises in MS analysis, we proposed a new approach of knowledge-integrated biomarker discovery using data from Major Adverse Cardiac Events (MACE) patients. We first built up a cardiovascular-related network based on protein information coming from protein annotations in Uniprot, protein–protein interaction (PPI), and signal transduction database. Distinct from the previous machine learning methods in MS data processing, we then used statistical methods to discover biomarkers in cardiovascular-related network. Through the tradeoff between known protein information and data noises in mass spectrometry data, we finally could firmly identify those high-confident biomarkers. Most importantly, aided by protein–protein interaction network, that is, cardiovascular-related network, we proposed a new type of biomarkers, that is, network biomarkers, composed of a set of proteins and the interactions among them. The candidate network biomarkers can classify the two groups of patients more accurately than current single ones without consideration of biological molecular interaction. PMID:18665624

A graph-theoretical analysis algorithm for quantifying the transition from sensory input to motor output by an emotional stimulus.

PubMed

Karmonik, Christof; Fung, Steve H; Dulay, M; Verma, A; Grossman, Robert G

2013-01-01

Graph-theoretical analysis algorithms have been used for identifying subnetworks in the human brain during the Default Mode State. Here, these methods are expanded to determine the interaction of the sensory and the motor subnetworks during the performance of an approach-avoidance paradigm utilizing the correlation strength between the signal intensity time courses as measure of synchrony. From functional magnetic resonance imaging (fMRI) data of 9 healthy volunteers, two signal time courses, one from the primary visual cortex (sensory input) and one from the motor cortex (motor output) were identified and a correlation difference map was calculated. Graph networks were created from this map and visualized with spring-embedded layouts and 3D layouts in the original anatomical space. Functional clusters in these networks were identified with the MCODE clustering algorithm. Interactions between the sensory sub-network and the motor sub-network were quantified through the interaction strengths of these clusters. The percentages of interactions involving the visual cortex ranged from 85 % to 18 % and the motor cortex ranged from 40 % to 9 %. Other regions with high interactions were: frontal cortex (19 ± 18 %), insula (17 ± 22 %), cuneus (16 ± 15 %), supplementary motor area (SMA, 11 ± 18 %) and subcortical regions (11 ± 10 %). Interactions between motor cortex, SMA and visual cortex accounted for 12 %, between visual cortex and cuneus for 8 % and between motor cortex, SMA and cuneus for 6 % of all interactions. These quantitative findings are supported by the visual impressions from the 2D and 3D network layouts.

Measuring Asymmetric Interactions in Resting State Brain Networks*

PubMed Central

Joshi, Anand A.; Salloum, Ronald; Bhushan, Chitresh; Leahy, Richard M.

2015-01-01

Directed graph representations of brain networks are increasingly being used in brain image analysis to indicate the direction and level of influence among brain regions. Most of the existing techniques for directed graph representations are based on time series analysis and the concept of causality, and use time lag information in the brain signals. These time lag-based techniques can be inadequate for functional magnetic resonance imaging (fMRI) signal analysis due to the limited time resolution of fMRI as well as the low frequency hemodynamic response. The aim of this paper is to present a novel measure of necessity that uses asymmetry in the joint distribution of brain activations to infer the direction and level of interaction among brain regions. We present a mathematical formula for computing necessity and extend this measure to partial necessity, which can potentially distinguish between direct and indirect interactions. These measures do not depend on time lag for directed modeling of brain interactions and therefore are more suitable for fMRI signal analysis. The necessity measures were used to analyze resting state fMRI data to determine the presence of hierarchy and asymmetry of brain interactions during resting state. We performed ROI-wise analysis using the proposed necessity measures to study the default mode network. The empirical joint distribution of the fMRI signals was determined using kernel density estimation, and was used for computation of the necessity and partial necessity measures. The significance of these measures was determined using a one-sided Wilcoxon rank-sum test. Our results are consistent with the hypothesis that the posterior cingulate cortex plays a central role in the default mode network. PMID:26221690

Variations in Social Network Type Membership Among Older African Americans, Caribbean Blacks, and Non-Hispanic Whites.

PubMed

Nguyen, Ann W

2017-07-01

This study examined race differences in the probability of belonging to a specific social network typology of family, friends, and church members. Samples of African Americans, Caribbean blacks, and non-Hispanic whites aged 55+ were drawn from the National Survey of American Life. Typology indicators related to social integration and negative interactions with family, friendship, and church networks were used. Latent class analysis was used to identify typologies, and latent class multinomial logistic regression was used to assess the influence of race, and interactions between race and age, and race and education on typology membership. Four network typologies were identified: optimal (high social integration, low negative interaction), family-centered (high social integration within primarily the extended family network, low negative interaction), strained (low social integration, high negative interaction), and ambivalent (high social integration and high negative interaction). Findings for race and age and race and education interactions indicated that the effects of education and age on typology membership varied by race. Overall, the findings demonstrate how race interacts with age and education to influence the probability of belonging to particular network types. A better understanding of the influence of race, education, and age on social network typologies will inform future research and theoretical developments in this area. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

How social network analysis can be used to monitor online collaborative learning and guide an informed intervention

PubMed Central

Fors, Uno; Tedre, Matti; Nouri, Jalal

2018-01-01

To ensure online collaborative learning meets the intended pedagogical goals (is actually collaborative and stimulates learning), mechanisms are needed for monitoring the efficiency of online collaboration. Various studies have indicated that social network analysis can be particularly effective in studying students’ interactions in online collaboration. However, research in education has only focused on the theoretical potential of using SNA, not on the actual benefits they achieved. This study investigated how social network analysis can be used to monitor online collaborative learning, find aspects in need of improvement, guide an informed intervention, and assess the efficacy of intervention using an experimental, observational repeated-measurement design in three courses over a full-term duration. Using a combination of SNA-based visual and quantitative analysis, we monitored three SNA constructs for each participant: the level of interactivity, the role, and position in information exchange, and the role played by each participant in the collaboration. On the group level, we monitored interactivity and group cohesion indicators. Our monitoring uncovered a non-collaborative teacher-centered pattern of interactions in the three studied courses as well as very few interactions among students, limited information exchange or negotiation, and very limited student networks dominated by the teacher. An intervention based on SNA-generated insights was designed. The intervention was structured into five actions: increasing awareness, promoting collaboration, improving the content, preparing teachers, and finally practicing with feedback. Evaluation of the intervention revealed that it has significantly enhanced student-student interactions and teacher-student interactions, as well as produced a collaborative pattern of interactions among most students and teachers. Since efficient and communicative activities are essential prerequisites for successful content discussion and for realizing the goals of collaboration, we suggest that our SNA-based approach will positively affect teaching and learning in many educational domains. Our study offers a proof-of-concept of what SNA can add to the current tools for monitoring and supporting teaching and learning in higher education. PMID:29566058

How social network analysis can be used to monitor online collaborative learning and guide an informed intervention.

PubMed

Saqr, Mohammed; Fors, Uno; Tedre, Matti; Nouri, Jalal

2018-01-01

To ensure online collaborative learning meets the intended pedagogical goals (is actually collaborative and stimulates learning), mechanisms are needed for monitoring the efficiency of online collaboration. Various studies have indicated that social network analysis can be particularly effective in studying students' interactions in online collaboration. However, research in education has only focused on the theoretical potential of using SNA, not on the actual benefits they achieved. This study investigated how social network analysis can be used to monitor online collaborative learning, find aspects in need of improvement, guide an informed intervention, and assess the efficacy of intervention using an experimental, observational repeated-measurement design in three courses over a full-term duration. Using a combination of SNA-based visual and quantitative analysis, we monitored three SNA constructs for each participant: the level of interactivity, the role, and position in information exchange, and the role played by each participant in the collaboration. On the group level, we monitored interactivity and group cohesion indicators. Our monitoring uncovered a non-collaborative teacher-centered pattern of interactions in the three studied courses as well as very few interactions among students, limited information exchange or negotiation, and very limited student networks dominated by the teacher. An intervention based on SNA-generated insights was designed. The intervention was structured into five actions: increasing awareness, promoting collaboration, improving the content, preparing teachers, and finally practicing with feedback. Evaluation of the intervention revealed that it has significantly enhanced student-student interactions and teacher-student interactions, as well as produced a collaborative pattern of interactions among most students and teachers. Since efficient and communicative activities are essential prerequisites for successful content discussion and for realizing the goals of collaboration, we suggest that our SNA-based approach will positively affect teaching and learning in many educational domains. Our study offers a proof-of-concept of what SNA can add to the current tools for monitoring and supporting teaching and learning in higher education.

FACETS: multi-faceted functional decomposition of protein interaction networks

PubMed Central

Seah, Boon-Siew; Bhowmick, Sourav S.; Forbes Dewey, C.

2012-01-01

Motivation: The availability of large-scale curated protein interaction datasets has given rise to the opportunity to investigate higher level organization and modularity within the protein–protein interaction (PPI) network using graph theoretic analysis. Despite the recent progress, systems level analysis of high-throughput PPIs remains a daunting task because of the amount of data they present. In this article, we propose a novel PPI network decomposition algorithm called FACETS in order to make sense of the deluge of interaction data using Gene Ontology (GO) annotations. FACETS finds not just a single functional decomposition of the PPI network, but a multi-faceted atlas of functional decompositions that portray alternative perspectives of the functional landscape of the underlying PPI network. Each facet in the atlas represents a distinct interpretation of how the network can be functionally decomposed and organized. Our algorithm maximizes interpretative value of the atlas by optimizing inter-facet orthogonality and intra-facet cluster modularity. Results: We tested our algorithm on the global networks from IntAct, and compared it with gold standard datasets from MIPS and KEGG. We demonstrated the performance of FACETS. We also performed a case study that illustrates the utility of our approach. Contact: seah0097@ntu.edu.sg or assourav@ntu.edu.sg Supplementary information: Supplementary data are available at the Bioinformatics online. Availability: Our software is available freely for non-commercial purposes from: http://www.cais.ntu.edu.sg/∼assourav/Facets/ PMID:22908217

Controllability analysis of the directed human protein interaction network identifies disease genes and drug targets

PubMed Central

Vinayagam, Arunachalam; Gibson, Travis E.; Lee, Ho-Joon; Yilmazel, Bahar; Roesel, Charles; Hu, Yanhui; Kwon, Young; Sharma, Amitabh; Liu, Yang-Yu; Perrimon, Norbert; Barabási, Albert-László

2016-01-01

The protein–protein interaction (PPI) network is crucial for cellular information processing and decision-making. With suitable inputs, PPI networks drive the cells to diverse functional outcomes such as cell proliferation or cell death. Here, we characterize the structural controllability of a large directed human PPI network comprising 6,339 proteins and 34,813 interactions. This network allows us to classify proteins as “indispensable,” “neutral,” or “dispensable,” which correlates to increasing, no effect, or decreasing the number of driver nodes in the network upon removal of that protein. We find that 21% of the proteins in the PPI network are indispensable. Interestingly, these indispensable proteins are the primary targets of disease-causing mutations, human viruses, and drugs, suggesting that altering a network’s control property is critical for the transition between healthy and disease states. Furthermore, analyzing copy number alterations data from 1,547 cancer patients reveals that 56 genes that are frequently amplified or deleted in nine different cancers are indispensable. Among the 56 genes, 46 of them have not been previously associated with cancer. This suggests that controllability analysis is very useful in identifying novel disease genes and potential drug targets. PMID:27091990

Network-Based Comparative Analysis of Arabidopsis Immune Responses to Golovinomyces orontii and Botrytis cinerea Infections.

PubMed

Jiang, Zhenhong; Dong, Xiaobao; Zhang, Ziding

2016-01-11

A comprehensive exploration of common and specific plant responses to biotrophs and necrotrophs is necessary for a better understanding of plant immunity. Here, we compared the Arabidopsis defense responses evoked by the biotrophic fungus Golovinomyces orontii and the necrotrophic fungus Botrytis cinerea through integrative network analysis. Two time-course transcriptional datasets were integrated with an Arabidopsis protein-protein interaction (PPI) network to construct a G. orontii conditional PPI sub-network (gCPIN) and a B. cinerea conditional PPI sub-network (bCPIN). We found that hubs in gCPIN and bCPIN played important roles in disease resistance. Hubs in bCPIN evolved faster than hubs in gCPIN, indicating the different selection pressures imposed on plants by different pathogens. By analyzing the common network from gCPIN and bCPIN, we identified two network components in which the genes were heavily involved in defense and development, respectively. The co-expression relationships between interacting proteins connecting the two components were different under G. orontii and B. cinerea infection conditions. Closer inspection revealed that auxin-related genes were overrepresented in the interactions connecting these two components, suggesting a critical role of auxin signaling in regulating the different co-expression relationships. Our work may provide new insights into plant defense responses against pathogens with different lifestyles.

Network Analysis of Protein Adaptation: Modeling the Functional Impact of Multiple Mutations

PubMed Central

Beleva Guthrie, Violeta; Masica, David L; Fraser, Andrew; Federico, Joseph; Fan, Yunfan; Camps, Manel; Karchin, Rachel

2018-01-01

Abstract The evolution of new biochemical activities frequently involves complex dependencies between mutations and rapid evolutionary radiation. Mutation co-occurrence and covariation have previously been used to identify compensating mutations that are the result of physical contacts and preserve protein function and fold. Here, we model pairwise functional dependencies and higher order interactions that enable evolution of new protein functions. We use a network model to find complex dependencies between mutations resulting from evolutionary trade-offs and pleiotropic effects. We present a method to construct these networks and to identify functionally interacting mutations in both extant and reconstructed ancestral sequences (Network Analysis of Protein Adaptation). The time ordering of mutations can be incorporated into the networks through phylogenetic reconstruction. We apply NAPA to three distantly homologous β-lactamase protein clusters (TEM, CTX-M-3, and OXA-51), each of which has experienced recent evolutionary radiation under substantially different selective pressures. By analyzing the network properties of each protein cluster, we identify key adaptive mutations, positive pairwise interactions, different adaptive solutions to the same selective pressure, and complex evolutionary trajectories likely to increase protein fitness. We also present evidence that incorporating information from phylogenetic reconstruction and ancestral sequence inference can reduce the number of spurious links in the network, whereas preserving overall network community structure. The analysis does not require structural or biochemical data. In contrast to function-preserving mutation dependencies, which are frequently from structural contacts, gain-of-function mutation dependencies are most commonly between residues distal in protein structure. PMID:29522102

BioLayout(Java): versatile network visualisation of structural and functional relationships.

PubMed

Goldovsky, Leon; Cases, Ildefonso; Enright, Anton J; Ouzounis, Christos A

2005-01-01

Visualisation of biological networks is becoming a common task for the analysis of high-throughput data. These networks correspond to a wide variety of biological relationships, such as sequence similarity, metabolic pathways, gene regulatory cascades and protein interactions. We present a general approach for the representation and analysis of networks of variable type, size and complexity. The application is based on the original BioLayout program (C-language implementation of the Fruchterman-Rheingold layout algorithm), entirely re-written in Java to guarantee portability across platforms. BioLayout(Java) provides broader functionality, various analysis techniques, extensions for better visualisation and a new user interface. Examples of analysis of biological networks using BioLayout(Java) are presented.

Friends, Depressive Symptoms, and Life Satisfaction Among Older Korean Americans.

PubMed

Roh, Soonhee; Lee, Yeon-Shim; Lee, Kyoung Hag; Shibusawa, Tazuko; Yoo, Grace J

2015-08-01

This study examined the interactive effects of social network support and depressive symptoms on life satisfaction among older Korean Americans (KAs). Using data from a sample of 200 elders in a large metropolitan area (M age = 72.50, SD = 5.15), hierarchical regression analysis was used to examine the interaction between social network support and depressive symptoms on life satisfaction among older KAs. After controlling for demographic variables, both social network support and depressive symptoms were identified as predictors for life satisfaction. Interaction effects indicated strong associations between higher social network support specifically from friends and lower depressive symptoms with higher levels of life satisfaction. Findings highlight the important role that friends play in terms of social network support for the mental health of older KAs, and the need for geriatric practitioners to monitor and assess the quality of social network support-including friendships-when working with older KAs.

Covering #SAE: A Mobile Reporting Class's Changing Patterns of Interaction on Twitter over Time

ERIC Educational Resources Information Center

Jones, Julie

2015-01-01

This study examined the social network that emerged on Twitter surrounding a mobile reporting class as they covered a national breaking news event. The work introduces pedagogical strategies that enhance students' learning opportunities. Through NodeXL and social network cluster analysis, six groups emerged from the Twitter interactions tied to…

Student Engagement and Affordances for Interaction with Diverse Peers: A Network Analysis

ERIC Educational Resources Information Center

Glass, Kimberly; Glass, Chris R.; Lynch, R. Jason

2016-01-01

This study utilized a network model in order to explore the relationship between patterns of student engagement and affordances for interaction with diverse peers for 12,852 students at 7 universities. The institutions are similar in type and size, with relatively moderate levels of structural racial diversity, and a range of overall…

Analysing Interactions in a Teacher Network Forum: A Sociometric Approach

ERIC Educational Resources Information Center

Lisboa, Eliana Santana; Coutinho, Clara Pereira

2013-01-01

This article presents the sociometric analysis of the interactions in a forum of a social network created for the professional development of Portuguese-speaking teachers. The main goal of the forum, which was titled Stricto Sensu, was to discuss the educational value of programmes that joined the distance learning model in Brazil. The empirical…

The Social Networks of Children With and Without Disabilities in Early Childhood Special Education Classrooms.

PubMed

Chen, Jing; Lin, Tzu-Jung; Justice, Laura; Sawyer, Brook

2017-09-01

Interaction with peers is an important contributor to young children's social and cognitive development. Yet, little is known about the nature of social networks within preschool inclusive classrooms. The current study applied a social network analysis to characterize children's peer interactions in inclusive classrooms and their relations with children's disability status. The participants were 485 preschoolers from 64 early childhood special education (ECSE) inclusive classrooms. Results from teachers' report of children's social networks showed that children with disabilities formed smaller play networks compared to their typically developing peers in the classroom, but no evidence indicated that children with disabilities engaged in more conflict networks than their counterparts. Children's play and conflict networks were segregated by children's disability status.

Internet-Based Approaches to Building Stakeholder Networks for Conservation and Natural Resource Management

EPA Science Inventory

Social network analysis (SNA) is based on a conceptual network representation of social interactions and is an invaluable tool for conservation professionals to increase collaboration, improve information flow, and increase efficiency. We present two approaches to constructing i...

Internet-Based Approaches to Building Stakeholder Networks for Conservation and Natural Resource Management.

EPA Science Inventory

Social network analysis (SNA) is based on a conceptual network representation of social interactions and is an invaluable tool for conservation professionals to increase collaboration, improve information flow, and increase efficiency. We present two approaches to constructing in...

Regulatory gene networks and the properties of the developmental process

NASA Technical Reports Server (NTRS)

Davidson, Eric H.; McClay, David R.; Hood, Leroy

2003-01-01

Genomic instructions for development are encoded in arrays of regulatory DNA. These specify large networks of interactions among genes producing transcription factors and signaling components. The architecture of such networks both explains and predicts developmental phenomenology. Although network analysis is yet in its early stages, some fundamental commonalities are already emerging. Two such are the use of multigenic feedback loops to ensure the progressivity of developmental regulatory states and the prevalence of repressive regulatory interactions in spatial control processes. Gene regulatory networks make it possible to explain the process of development in causal terms and eventually will enable the redesign of developmental regulatory circuitry to achieve different outcomes.

Comparing Networks from a Data Analysis Perspective

NASA Astrophysics Data System (ADS)

Li, Wei; Yang, Jing-Yu

To probe network characteristics, two predominant ways of network comparison are global property statistics and subgraph enumeration. However, they suffer from limited information and exhaustible computing. Here, we present an approach to compare networks from the perspective of data analysis. Initially, the approach projects each node of original network as a high-dimensional data point, and the network is seen as clouds of data points. Then the dispersion information of the principal component analysis (PCA) projection of the generated data clouds can be used to distinguish networks. We applied this node projection method to the yeast protein-protein interaction networks and the Internet Autonomous System networks, two types of networks with several similar higher properties. The method can efficiently distinguish one from the other. The identical result of different datasets from independent sources also indicated that the method is a robust and universal framework.

The Influence of Gender, Age, Matriline and Hierarchical Rank on Individual Social Position, Role and Interactional Patterns in Macaca sylvanus at ‘La Forêt des Singes’: A Multilevel Social Network Approach

PubMed Central

Sosa, Sebastian

2016-01-01

A society is a complex system composed of individuals that can be characterized by their own attributes that influence their behaviors. In this study, a specific analytical protocol based on social network analysis was adopted to investigate the influence of four attributes (gender, age, matriline, and hierarchical rank) on affiliative (allogrooming) and agonistic networks in a non-human primate species, Macaca sylvanus, at the park La Forêt des Singes in France. The results show significant differences with respect to the position (i.e., centric, peripheral) and role (i.e., implication in the network cohesiveness) of an individual within a social network and hence interactional patterns. Females are more central, more active, and have a denser ego network in the affiliative social network tan males; thus, they contribute in a greater way to the cohesive structure of the network. High-ranking individuals are likely to receive fewer agonistic behaviors than low-ranking individuals, and high-ranking females receive more allogrooming. I also observe homophily for affiliative interactions regarding all attributes and homophily for agonistic interactions regarding gender and age. Revealing the positions, the roles, and the interactional behavioral patterns of individuals can help understand the mechanisms that shape the overall structure of a social network. PMID:27148137

The Influence of Gender, Age, Matriline and Hierarchical Rank on Individual Social Position, Role and Interactional Patterns in Macaca sylvanus at 'La Forêt des Singes': A Multilevel Social Network Approach.

PubMed

Sosa, Sebastian

2016-01-01

A society is a complex system composed of individuals that can be characterized by their own attributes that influence their behaviors. In this study, a specific analytical protocol based on social network analysis was adopted to investigate the influence of four attributes (gender, age, matriline, and hierarchical rank) on affiliative (allogrooming) and agonistic networks in a non-human primate species, Macaca sylvanus, at the park La Forêt des Singes in France. The results show significant differences with respect to the position (i.e., centric, peripheral) and role (i.e., implication in the network cohesiveness) of an individual within a social network and hence interactional patterns. Females are more central, more active, and have a denser ego network in the affiliative social network tan males; thus, they contribute in a greater way to the cohesive structure of the network. High-ranking individuals are likely to receive fewer agonistic behaviors than low-ranking individuals, and high-ranking females receive more allogrooming. I also observe homophily for affiliative interactions regarding all attributes and homophily for agonistic interactions regarding gender and age. Revealing the positions, the roles, and the interactional behavioral patterns of individuals can help understand the mechanisms that shape the overall structure of a social network.

Mining protein-protein interaction networks: denoising effects

NASA Astrophysics Data System (ADS)

Marras, Elisabetta; Capobianco, Enrico

2009-01-01

A typical instrument to pursue analysis in complex network studies is the analysis of the statistical distributions. They are usually computed for measures which characterize network topology, and are aimed at capturing both structural and dynamics aspects. Protein-protein interaction networks (PPIN) have also been studied through several measures. It is in general observed that a power law is expected to characterize scale-free networks. However, mixing the original noise cover with outlying information and other system-dependent fluctuations makes the empirical detection of the power law a difficult task. As a result the uncertainty level increases when looking at the observed sample; in particular, one may wonder whether the computed features may be sufficient to explain the interactome. We then address noise problems by implementing both decomposition and denoising techniques that reduce the impact of factors known to affect the accuracy of power law detection.

A Small World of Neuronal Synchrony

PubMed Central

Yu, Shan; Huang, Debin; Singer, Wolf

2008-01-01

A small-world network has been suggested to be an efficient solution for achieving both modular and global processing—a property highly desirable for brain computations. Here, we investigated functional networks of cortical neurons using correlation analysis to identify functional connectivity. To reconstruct the interaction network, we applied the Ising model based on the principle of maximum entropy. This allowed us to assess the interactions by measuring pairwise correlations and to assess the strength of coupling from the degree of synchrony. Visual responses were recorded in visual cortex of anesthetized cats, simultaneously from up to 24 neurons. First, pairwise correlations captured most of the patterns in the population's activity and, therefore, provided a reliable basis for the reconstruction of the interaction networks. Second, and most importantly, the resulting networks had small-world properties; the average path lengths were as short as in simulated random networks, but the clustering coefficients were larger. Neurons differed considerably with respect to the number and strength of interactions, suggesting the existence of “hubs” in the network. Notably, there was no evidence for scale-free properties. These results suggest that cortical networks are optimized for the coexistence of local and global computations: feature detection and feature integration or binding. PMID:18400792

Understanding interactions in virtual HIV communities: a social network analysis approach.

PubMed

Shi, Jingyuan; Wang, Xiaohui; Peng, Tai-Quan; Chen, Liang

2017-02-01

This study investigated the driving mechanism of building interaction ties among the people living with HIV/AIDS in one of the largest virtual HIV communities in China using social network analysis. Specifically, we explained the probability of forming interaction ties with homophily and popularity characteristics. The exponential random graph modeling results showed that members in this community tend to form homophilous ties in terms of shared location and interests. Moreover, we found a tendency away from popularity effect. This suggests that in this community, resources and information were not disproportionally received by a few of members, which could be beneficial to the overall community.

System-level insights into the cellular interactome of a non-model organism: inferring, modelling and analysing functional gene network of soybean (Glycine max).

PubMed

Xu, Yungang; Guo, Maozu; Zou, Quan; Liu, Xiaoyan; Wang, Chunyu; Liu, Yang

2014-01-01

Cellular interactome, in which genes and/or their products interact on several levels, forming transcriptional regulatory-, protein interaction-, metabolic-, signal transduction networks, etc., has attracted decades of research focuses. However, such a specific type of network alone can hardly explain the various interactive activities among genes. These networks characterize different interaction relationships, implying their unique intrinsic properties and defects, and covering different slices of biological information. Functional gene network (FGN), a consolidated interaction network that models fuzzy and more generalized notion of gene-gene relations, have been proposed to combine heterogeneous networks with the goal of identifying functional modules supported by multiple interaction types. There are yet no successful precedents of FGNs on sparsely studied non-model organisms, such as soybean (Glycine max), due to the absence of sufficient heterogeneous interaction data. We present an alternative solution for inferring the FGNs of soybean (SoyFGNs), in a pioneering study on the soybean interactome, which is also applicable to other organisms. SoyFGNs exhibit the typical characteristics of biological networks: scale-free, small-world architecture and modularization. Verified by co-expression and KEGG pathways, SoyFGNs are more extensive and accurate than an orthology network derived from Arabidopsis. As a case study, network-guided disease-resistance gene discovery indicates that SoyFGNs can provide system-level studies on gene functions and interactions. This work suggests that inferring and modelling the interactome of a non-model plant are feasible. It will speed up the discovery and definition of the functions and interactions of other genes that control important functions, such as nitrogen fixation and protein or lipid synthesis. The efforts of the study are the basis of our further comprehensive studies on the soybean functional interactome at the genome and microRNome levels. Additionally, a web tool for information retrieval and analysis of SoyFGNs can be accessed at SoyFN: http://nclab.hit.edu.cn/SoyFN.

System-Level Insights into the Cellular Interactome of a Non-Model Organism: Inferring, Modelling and Analysing Functional Gene Network of Soybean (Glycine max)

PubMed Central

Xu, Yungang; Guo, Maozu; Zou, Quan; Liu, Xiaoyan; Wang, Chunyu; Liu, Yang

2014-01-01

Cellular interactome, in which genes and/or their products interact on several levels, forming transcriptional regulatory-, protein interaction-, metabolic-, signal transduction networks, etc., has attracted decades of research focuses. However, such a specific type of network alone can hardly explain the various interactive activities among genes. These networks characterize different interaction relationships, implying their unique intrinsic properties and defects, and covering different slices of biological information. Functional gene network (FGN), a consolidated interaction network that models fuzzy and more generalized notion of gene-gene relations, have been proposed to combine heterogeneous networks with the goal of identifying functional modules supported by multiple interaction types. There are yet no successful precedents of FGNs on sparsely studied non-model organisms, such as soybean (Glycine max), due to the absence of sufficient heterogeneous interaction data. We present an alternative solution for inferring the FGNs of soybean (SoyFGNs), in a pioneering study on the soybean interactome, which is also applicable to other organisms. SoyFGNs exhibit the typical characteristics of biological networks: scale-free, small-world architecture and modularization. Verified by co-expression and KEGG pathways, SoyFGNs are more extensive and accurate than an orthology network derived from Arabidopsis. As a case study, network-guided disease-resistance gene discovery indicates that SoyFGNs can provide system-level studies on gene functions and interactions. This work suggests that inferring and modelling the interactome of a non-model plant are feasible. It will speed up the discovery and definition of the functions and interactions of other genes that control important functions, such as nitrogen fixation and protein or lipid synthesis. The efforts of the study are the basis of our further comprehensive studies on the soybean functional interactome at the genome and microRNome levels. Additionally, a web tool for information retrieval and analysis of SoyFGNs can be accessed at SoyFN: http://nclab.hit.edu.cn/SoyFN. PMID:25423109

Discovery of Information Diffusion Process in Social Networks

NASA Astrophysics Data System (ADS)

Kim, Kwanho; Jung, Jae-Yoon; Park, Jonghun

Information diffusion analysis in social networks is of significance since it enables us to deeply understand dynamic social interactions among users. In this paper, we introduce approaches to discovering information diffusion process in social networks based on process mining. Process mining techniques are applied from three perspectives: social network analysis, process discovery and community recognition. We then present experimental results by using a real-life social network data. The proposed techniques are expected to employ as new analytical tools in online social networks such as blog and wikis for company marketers, politicians, news reporters and online writers.

CUFID-query: accurate network querying through random walk based network flow estimation.

PubMed

Jeong, Hyundoo; Qian, Xiaoning; Yoon, Byung-Jun

2017-12-28

Functional modules in biological networks consist of numerous biomolecules and their complicated interactions. Recent studies have shown that biomolecules in a functional module tend to have similar interaction patterns and that such modules are often conserved across biological networks of different species. As a result, such conserved functional modules can be identified through comparative analysis of biological networks. In this work, we propose a novel network querying algorithm based on the CUFID (Comparative network analysis Using the steady-state network Flow to IDentify orthologous proteins) framework combined with an efficient seed-and-extension approach. The proposed algorithm, CUFID-query, can accurately detect conserved functional modules as small subnetworks in the target network that are expected to perform similar functions to the given query functional module. The CUFID framework was recently developed for probabilistic pairwise global comparison of biological networks, and it has been applied to pairwise global network alignment, where the framework was shown to yield accurate network alignment results. In the proposed CUFID-query algorithm, we adopt the CUFID framework and extend it for local network alignment, specifically to solve network querying problems. First, in the seed selection phase, the proposed method utilizes the CUFID framework to compare the query and the target networks and to predict the probabilistic node-to-node correspondence between the networks. Next, the algorithm selects and greedily extends the seed in the target network by iteratively adding nodes that have frequent interactions with other nodes in the seed network, in a way that the conductance of the extended network is maximally reduced. Finally, CUFID-query removes irrelevant nodes from the querying results based on the personalized PageRank vector for the induced network that includes the fully extended network and its neighboring nodes. Through extensive performance evaluation based on biological networks with known functional modules, we show that CUFID-query outperforms the existing state-of-the-art algorithms in terms of prediction accuracy and biological significance of the predictions.

Unified functional network and nonlinear time series analysis for complex systems science: The pyunicorn package

NASA Astrophysics Data System (ADS)

Donges, Jonathan F.; Heitzig, Jobst; Beronov, Boyan; Wiedermann, Marc; Runge, Jakob; Feng, Qing Yi; Tupikina, Liubov; Stolbova, Veronika; Donner, Reik V.; Marwan, Norbert; Dijkstra, Henk A.; Kurths, Jürgen

2015-11-01

We introduce the pyunicorn (Pythonic unified complex network and recurrence analysis toolbox) open source software package for applying and combining modern methods of data analysis and modeling from complex network theory and nonlinear time series analysis. pyunicorn is a fully object-oriented and easily parallelizable package written in the language Python. It allows for the construction of functional networks such as climate networks in climatology or functional brain networks in neuroscience representing the structure of statistical interrelationships in large data sets of time series and, subsequently, investigating this structure using advanced methods of complex network theory such as measures and models for spatial networks, networks of interacting networks, node-weighted statistics, or network surrogates. Additionally, pyunicorn provides insights into the nonlinear dynamics of complex systems as recorded in uni- and multivariate time series from a non-traditional perspective by means of recurrence quantification analysis, recurrence networks, visibility graphs, and construction of surrogate time series. The range of possible applications of the library is outlined, drawing on several examples mainly from the field of climatology.

Exploring pathway interactions in insulin resistant mouse liver

PubMed Central

2011-01-01

Background Complex phenotypes such as insulin resistance involve different biological pathways that may interact and influence each other. Interpretation of related experimental data would be facilitated by identifying relevant pathway interactions in the context of the dataset. Results We developed an analysis approach to study interactions between pathways by integrating gene and protein interaction networks, biological pathway information and high-throughput data. This approach was applied to a transcriptomics dataset to investigate pathway interactions in insulin resistant mouse liver in response to a glucose challenge. We identified regulated pathway interactions at different time points following the glucose challenge and also studied the underlying protein interactions to find possible mechanisms and key proteins involved in pathway cross-talk. A large number of pathway interactions were found for the comparison between the two diet groups at t = 0. The initial response to the glucose challenge (t = 0.6) was typed by an acute stress response and pathway interactions showed large overlap between the two diet groups, while the pathway interaction networks for the late response were more dissimilar. Conclusions Studying pathway interactions provides a new perspective on the data that complements established pathway analysis methods such as enrichment analysis. This study provided new insights in how interactions between pathways may be affected by insulin resistance. In addition, the analysis approach described here can be generally applied to different types of high-throughput data and will therefore be useful for analysis of other complex datasets as well. PMID:21843341

Talking and learning physics: Predicting future grades from network measures and Force Concept Inventory pretest scores

NASA Astrophysics Data System (ADS)

Bruun, Jesper; Brewe, Eric

2013-12-01

The role of student interactions in learning situations is a foundation of sociocultural learning theory, and social network analysis can be used to quantify student relations. We discuss how self-reported student interactions can be viewed as processes of meaning making and use this to understand how quantitative measures that describe the position in a network, called centrality measures, can be understood in terms of interactions that happen in the context of a university physics course. We apply this discussion to an empirical data set of self-reported student interactions. In a weekly administered survey, first year university students enrolled in an introductory physics course at a Danish university indicated with whom they remembered having communicated within different interaction categories. For three categories pertaining to (1) communication about how to solve physics problems in the course (called the PS category), (2) communications about the nature of physics concepts (called the CD category), and (3) social interactions that are not strictly related to the content of the physics classes (called the ICS category) in the introductory mechanics course, we use the survey data to create networks of student interaction. For each of these networks, we calculate centrality measures for each student and correlate these measures with grades from the introductory course, grades from two subsequent courses, and the pretest Force Concept Inventory (FCI) scores. We find highly significant correlations (p<0.001) between network centrality measures and grades in all networks. We find the highest correlations between network centrality measures and future grades. In the network composed of interactions regarding problem solving (the PS network), the centrality measures hide and PageRank show the highest correlations (r=-0.32 and r=0.33, respectively) with future grades. In the CD network, the network measure target entropy shows the highest correlation (r=0.45) with future grades. In the network composed solely of noncontent related social interactions, these patterns of correlation are maintained in the sense that these network measures show the highest correlations and maintain their internal ranking. Using hierarchical linear regression, we find that a linear model that adds the network measures hide and target entropy, calculated on the ICS network, significantly improves a base model that uses only the FCI pretest scores from the beginning of the semester. Though one should not infer causality from these results, they do point to how social interactions in class are intertwined with academic interactions. We interpret this as an integral part of learning, and suggest that physics is a robust example.

Using Networks To Understand Medical Data: The Case of Class III Malocclusions

PubMed Central

Scala, Antonio; Auconi, Pietro; Scazzocchio, Marco; Caldarelli, Guido; McNamara, James A.; Franchi, Lorenzo

2012-01-01

A system of elements that interact or regulate each other can be represented by a mathematical object called a network. While network analysis has been successfully applied to high-throughput biological systems, less has been done regarding their application in more applied fields of medicine; here we show an application based on standard medical diagnostic data. We apply network analysis to Class III malocclusion, one of the most difficult to understand and treat orofacial anomaly. We hypothesize that different interactions of the skeletal components can contribute to pathological disequilibrium; in order to test this hypothesis, we apply network analysis to 532 Class III young female patients. The topology of the Class III malocclusion obtained by network analysis shows a strong co-occurrence of abnormal skeletal features. The pattern of these occurrences influences the vertical and horizontal balance of disharmony in skeletal form and position. Patients with more unbalanced orthodontic phenotypes show preponderance of the pathological skeletal nodes and minor relevance of adaptive dentoalveolar equilibrating nodes. Furthermore, by applying Power Graphs analysis we identify some functional modules among orthodontic nodes. These modules correspond to groups of tightly inter-related features and presumably constitute the key regulators of plasticity and the sites of unbalance of the growing dentofacial Class III system. The data of the present study show that, in their most basic abstraction level, the orofacial characteristics can be represented as graphs using nodes to represent orthodontic characteristics, and edges to represent their various types of interactions. The applications of this mathematical model could improve the interpretation of the quantitative, patient-specific information, and help to better targeting therapy. Last but not least, the methodology we have applied in analyzing orthodontic features can be applied easily to other fields of the medical science. PMID:23028552

Investigation of candidate genes for osteoarthritis based on gene expression profiles.

PubMed

Dong, Shuanghai; Xia, Tian; Wang, Lei; Zhao, Qinghua; Tian, Jiwei

2016-12-01

To explore the mechanism of osteoarthritis (OA) and provide valid biological information for further investigation. Gene expression profile of GSE46750 was downloaded from Gene Expression Omnibus database. The Linear Models for Microarray Data (limma) package (Bioconductor project, http://www.bioconductor.org/packages/release/bioc/html/limma.html) was used to identify differentially expressed genes (DEGs) in inflamed OA samples. Gene Ontology function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis of DEGs were performed based on Database for Annotation, Visualization and Integrated Discovery data, and protein-protein interaction (PPI) network was constructed based on the Search Tool for the Retrieval of Interacting Genes/Proteins database. Regulatory network was screened based on Encyclopedia of DNA Elements. Molecular Complex Detection was used for sub-network screening. Two sub-networks with highest node degree were integrated with transcriptional regulatory network and KEGG functional enrichment analysis was processed for 2 modules. In total, 401 up- and 196 down-regulated DEGs were obtained. Up-regulated DEGs were involved in inflammatory response, while down-regulated DEGs were involved in cell cycle. PPI network with 2392 protein interactions was constructed. Moreover, 10 genes including Interleukin 6 (IL6) and Aurora B kinase (AURKB) were found to be outstanding in PPI network. There are 214 up- and 8 down-regulated transcription factor (TF)-target pairs in the TF regulatory network. Module 1 had TFs including SPI1, PRDM1, and FOS, while module 2 contained FOSL1. The nodes in module 1 were enriched in chemokine signaling pathway, while the nodes in module 2 were mainly enriched in cell cycle. The screened DEGs including IL6, AGT, and AURKB might be potential biomarkers for gene therapy for OA by being regulated by TFs such as FOS and SPI1, and participating in the cell cycle and cytokine-cytokine receptor interaction pathway. Copyright © 2016 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.

Meta-review of protein network regulating obesity between validated obesity candidate genes in the white adipose tissue of high-fat diet-induced obese C57BL/6J mice.

PubMed

Kim, Eunjung; Kim, Eun Jung; Seo, Seung-Won; Hur, Cheol-Goo; McGregor, Robin A; Choi, Myung-Sook

2014-01-01

Worldwide obesity and related comorbidities are increasing, but identifying new therapeutic targets remains a challenge. A plethora of microarray studies in diet-induced obesity models has provided large datasets of obesity associated genes. In this review, we describe an approach to examine the underlying molecular network regulating obesity, and we discuss interactions between obesity candidate genes. We conducted network analysis on functional protein-protein interactions associated with 25 obesity candidate genes identified in a literature-driven approach based on published microarray studies of diet-induced obesity. The obesity candidate genes were closely associated with lipid metabolism and inflammation. Peroxisome proliferator activated receptor gamma (Pparg) appeared to be a core obesity gene, and obesity candidate genes were highly interconnected, suggesting a coordinately regulated molecular network in adipose tissue. In conclusion, the current network analysis approach may help elucidate the underlying molecular network regulating obesity and identify anti-obesity targets for therapeutic intervention.

Proteomic and computational analysis of bronchoalveolar proteins during the course of the acute respiratory distress syndrome.

PubMed

Chang, Dong W; Hayashi, Shinichi; Gharib, Sina A; Vaisar, Tomas; King, S Trevor; Tsuchiya, Mitsuhiro; Ruzinski, John T; Park, David R; Matute-Bello, Gustavo; Wurfel, Mark M; Bumgarner, Roger; Heinecke, Jay W; Martin, Thomas R

2008-10-01

Acute lung injury causes complex changes in protein expression in the lungs. Whereas most prior studies focused on single proteins, newer methods allowing the simultaneous study of many proteins could lead to a better understanding of pathogenesis and new targets for treatment. The purpose of this study was to examine the changes in protein expression in the bronchoalveolar lavage fluid (BALF) of patients during the course of the acute respiratory distress syndrome (ARDS). Using two-dimensional difference gel electrophoresis (DIGE), the expression of proteins in the BALF from patients on Days 1 (n = 7), 3 (n = 8), and 7 (n = 5) of ARDS were compared with findings in normal volunteers (n = 9). The patterns of protein expression were analyzed using principal component analysis (PCA). Biological processes that were enriched in the BALF proteins of patients with ARDS were identified using Gene Ontology (GO) analysis. Protein networks that model the protein interactions in the BALF were generated using Ingenuity Pathway Analysis. An average of 991 protein spots were detected using DIGE. Of these, 80 protein spots, representing 37 unique proteins in all of the fluids, were identified using mass spectrometry. PCA confirmed important differences between the proteins in the ARDS and normal samples. GO analysis showed that these differences are due to the enrichment of proteins involved in inflammation, infection, and injury. The protein network analysis showed that the protein interactions in ARDS are complex and redundant, and revealed unexpected central components in the protein networks. Proteomics and protein network analysis reveals the complex nature of lung protein interactions in ARDS. The results provide new insights about protein networks in injured lungs, and identify novel mediators that are likely to be involved in the pathogenesis and progression of acute lung injury.

NDEx: A Community Resource for Sharing and Publishing of Biological Networks.

PubMed

Pillich, Rudolf T; Chen, Jing; Rynkov, Vladimir; Welker, David; Pratt, Dexter

2017-01-01

Networks are a powerful and flexible paradigm that facilitate communication and computation about interactions of any type, whether social, economic, or biological. NDEx, the Network Data Exchange, is an online commons to enable new modes of collaboration and publication using biological networks. NDEx creates an access point and interface to a broad range of networks, whether they express molecular interactions, curated relationships from literature, or the outputs of systematic analysis of big data. Research organizations can use NDEx as a distribution channel for networks they generate or curate. Developers of bioinformatic applications can store and query NDEx networks via a common programmatic interface. NDEx can also facilitate the integration of networks as data in electronic publications, thus making a step toward an ecosystem in which networks bearing data, hypotheses, and findings flow seamlessly between scientists.

Multi-cultural Wikipedia mining of geopolitics interactions leveraging reduced Google matrix analysis

NASA Astrophysics Data System (ADS)

Frahm, Klaus M.; El Zant, Samer; Jaffrès-Runser, Katia; Shepelyansky, Dima L.

2017-09-01

Geopolitics focuses on political power in relation to geographic space. Interactions among world countries have been widely studied at various scales, observing economic exchanges, world history or international politics among others. This work exhibits the potential of Wikipedia mining for such studies. Indeed, Wikipedia stores valuable fine-grained dependencies among countries by linking webpages together for diverse types of interactions (not only related to economical, political or historical facts). We mine herein the Wikipedia networks of several language editions using the recently proposed method of reduced Google matrix analysis. This approach allows to establish direct and hidden links between a subset of nodes that belong to a much larger directed network. Our study concentrates on 40 major countries chosen worldwide. Our aim is to offer a multicultural perspective on their interactions by comparing networks extracted from five different Wikipedia language editions, emphasizing English, Russian and Arabic ones. We demonstrate that this approach allows to recover meaningful direct and hidden links among the 40 countries of interest.

A Method for Predicting Protein Complexes from Dynamic Weighted Protein-Protein Interaction Networks.

PubMed

Liu, Lizhen; Sun, Xiaowu; Song, Wei; Du, Chao

2018-06-01

Predicting protein complexes from protein-protein interaction (PPI) network is of great significance to recognize the structure and function of cells. A protein may interact with different proteins under different time or conditions. Existing approaches only utilize static PPI network data that may lose much temporal biological information. First, this article proposed a novel method that combines gene expression data at different time points with traditional static PPI network to construct different dynamic subnetworks. Second, to further filter out the data noise, the semantic similarity based on gene ontology is regarded as the network weight together with the principal component analysis, which is introduced to deal with the weight computing by three traditional methods. Third, after building a dynamic PPI network, a predicting protein complexes algorithm based on "core-attachment" structural feature is applied to detect complexes from each dynamic subnetworks. Finally, it is revealed from the experimental results that our method proposed in this article performs well on detecting protein complexes from dynamic weighted PPI networks.

An interactional network of genes involved in chitin synthesis in Saccharomyces cerevisiae.

PubMed

Lesage, Guillaume; Shapiro, Jesse; Specht, Charles A; Sdicu, Anne-Marie; Ménard, Patrice; Hussein, Shamiza; Tong, Amy Hin Yan; Boone, Charles; Bussey, Howard

2005-02-16

In S. cerevisiae the beta-1,4-linked N-acetylglucosamine polymer, chitin, is synthesized by a family of 3 specialized but interacting chitin synthases encoded by CHS1, CHS2 and CHS3. Chs2p makes chitin in the primary septum, while Chs3p makes chitin in the lateral cell wall and in the bud neck, and can partially compensate for the lack of Chs2p. Chs3p requires a pathway of Bni4p, Chs4p, Chs5p, Chs6p and Chs7p for its localization and activity. Chs1p is thought to have a septum repair function after cell separation. To further explore interactions in the chitin synthase family and to find processes buffering chitin synthesis, we compiled a genetic interaction network of genes showing synthetic interactions with CHS1, CHS3 and genes involved in Chs3p localization and function and made a phenotypic analysis of their mutants. Using deletion mutants in CHS1, CHS3, CHS4, CHS5, CHS6, CHS7 and BNI4 in a synthetic genetic array analysis we assembled a network of 316 interactions among 163 genes. The interaction network with CHS3, CHS4, CHS5, CHS6, CHS7 or BNI4 forms a dense neighborhood, with many genes functioning in cell wall assembly or polarized secretion. Chitin levels were altered in 54 of the mutants in individually deleted genes, indicating a functional relationship between them and chitin synthesis. 32 of these mutants triggered the chitin stress response, with elevated chitin levels and a dependence on CHS3. A large fraction of the CHS1-interaction set was distinct from that of the CHS3 network, indicating broad roles for Chs1p in buffering both Chs2p function and more global cell wall robustness. Based on their interaction patterns and chitin levels we group interacting mutants into functional categories. Genes interacting with CHS3 are involved in the amelioration of cell wall defects and in septum or bud neck chitin synthesis, and we newly assign a number of genes to these functions. Our genetic analysis of genes not interacting with CHS3 indicate expanded roles for Chs4p, Chs5p and Chs6p in secretory protein trafficking and of Bni4p in bud neck organization.

Building protein-protein interaction networks for Leishmania species through protein structural information.

PubMed

Dos Santos Vasconcelos, Crhisllane Rafaele; de Lima Campos, Túlio; Rezende, Antonio Mauro

2018-03-06

Systematic analysis of a parasite interactome is a key approach to understand different biological processes. It makes possible to elucidate disease mechanisms, to predict protein functions and to select promising targets for drug development. Currently, several approaches for protein interaction prediction for non-model species incorporate only small fractions of the entire proteomes and their interactions. Based on this perspective, this study presents an integration of computational methodologies, protein network predictions and comparative analysis of the protozoan species Leishmania braziliensis and Leishmania infantum. These parasites cause Leishmaniasis, a worldwide distributed and neglected disease, with limited treatment options using currently available drugs. The predicted interactions were obtained from a meta-approach, applying rigid body docking tests and template-based docking on protein structures predicted by different comparative modeling techniques. In addition, we trained a machine-learning algorithm (Gradient Boosting) using docking information performed on a curated set of positive and negative protein interaction data. Our final model obtained an AUC = 0.88, with recall = 0.69, specificity = 0.88 and precision = 0.83. Using this approach, it was possible to confidently predict 681 protein structures and 6198 protein interactions for L. braziliensis, and 708 protein structures and 7391 protein interactions for L. infantum. The predicted networks were integrated to protein interaction data already available, analyzed using several topological features and used to classify proteins as essential for network stability. The present study allowed to demonstrate the importance of integrating different methodologies of interaction prediction to increase the coverage of the protein interaction of the studied protocols, besides it made available protein structures and interactions not previously reported.

QuIN: A Web Server for Querying and Visualizing Chromatin Interaction Networks

PubMed Central

Thibodeau, Asa; Márquez, Eladio J.; Luo, Oscar; Ruan, Yijun; Shin, Dong-Guk; Stitzel, Michael L.; Ucar, Duygu

2016-01-01

Recent studies of the human genome have indicated that regulatory elements (e.g. promoters and enhancers) at distal genomic locations can interact with each other via chromatin folding and affect gene expression levels. Genomic technologies for mapping interactions between DNA regions, e.g., ChIA-PET and HiC, can generate genome-wide maps of interactions between regulatory elements. These interaction datasets are important resources to infer distal gene targets of non-coding regulatory elements and to facilitate prioritization of critical loci for important cellular functions. With the increasing diversity and complexity of genomic information and public ontologies, making sense of these datasets demands integrative and easy-to-use software tools. Moreover, network representation of chromatin interaction maps enables effective data visualization, integration, and mining. Currently, there is no software that can take full advantage of network theory approaches for the analysis of chromatin interaction datasets. To fill this gap, we developed a web-based application, QuIN, which enables: 1) building and visualizing chromatin interaction networks, 2) annotating networks with user-provided private and publicly available functional genomics and interaction datasets, 3) querying network components based on gene name or chromosome location, and 4) utilizing network based measures to identify and prioritize critical regulatory targets and their direct and indirect interactions. AVAILABILITY: QuIN’s web server is available at http://quin.jax.org QuIN is developed in Java and JavaScript, utilizing an Apache Tomcat web server and MySQL database and the source code is available under the GPLV3 license available on GitHub: https://github.com/UcarLab/QuIN/. PMID:27336171

GENOME-WIDE GENETIC INTERACTION ANALYSIS OF GLAUCOMA USING EXPERT KNOWLEDGE DERIVED FROM HUMAN PHENOTYPE NETWORKS

PubMed Central

HU, TING; DARABOS, CHRISTIAN; CRICCO, MARIA E.; KONG, EMILY; MOORE, JASON H.

2014-01-01

The large volume of GWAS data poses great computational challenges for analyzing genetic interactions associated with common human diseases. We propose a computational framework for characterizing epistatic interactions among large sets of genetic attributes in GWAS data. We build the human phenotype network (HPN) and focus around a disease of interest. In this study, we use the GLAUGEN glaucoma GWAS dataset and apply the HPN as a biological knowledge-based filter to prioritize genetic variants. Then, we use the statistical epistasis network (SEN) to identify a significant connected network of pairwise epistatic interactions among the prioritized SNPs. These clearly highlight the complex genetic basis of glaucoma. Furthermore, we identify key SNPs by quantifying structural network characteristics. Through functional annotation of these key SNPs using Biofilter, a software accessing multiple publicly available human genetic data sources, we find supporting biomedical evidences linking glaucoma to an array of genetic diseases, proving our concept. We conclude by suggesting hypotheses for a better understanding of the disease. PMID:25592582

Functional wiring of the yeast kinome revealed by global analysis of genetic network motifs

PubMed Central

Sharifpoor, Sara; van Dyk, Dewald; Costanzo, Michael; Baryshnikova, Anastasia; Friesen, Helena; Douglas, Alison C.; Youn, Ji-Young; VanderSluis, Benjamin; Myers, Chad L.; Papp, Balázs; Boone, Charles; Andrews, Brenda J.

2012-01-01

A combinatorial genetic perturbation strategy was applied to interrogate the yeast kinome on a genome-wide scale. We assessed the global effects of gene overexpression or gene deletion to map an integrated genetic interaction network of synthetic dosage lethal (SDL) and loss-of-function genetic interactions (GIs) for 92 kinases, producing a meta-network of 8700 GIs enriched for pathways known to be regulated by cognate kinases. Kinases most sensitive to dosage perturbations had constitutive cell cycle or cell polarity functions under standard growth conditions. Condition-specific screens confirmed that the spectrum of kinase dosage interactions can be expanded substantially in activating conditions. An integrated network composed of systematic SDL, negative and positive loss-of-function GIs, and literature-curated kinase–substrate interactions revealed kinase-dependent regulatory motifs predictive of novel gene-specific phenotypes. Our study provides a valuable resource to unravel novel functional relationships and pathways regulated by kinases and outlines a general strategy for deciphering mutant phenotypes from large-scale GI networks. PMID:22282571

Genes2Networks: connecting lists of gene symbols using mammalian protein interactions databases.

PubMed

Berger, Seth I; Posner, Jeremy M; Ma'ayan, Avi

2007-10-04

In recent years, mammalian protein-protein interaction network databases have been developed. The interactions in these databases are either extracted manually from low-throughput experimental biomedical research literature, extracted automatically from literature using techniques such as natural language processing (NLP), generated experimentally using high-throughput methods such as yeast-2-hybrid screens, or interactions are predicted using an assortment of computational approaches. Genes or proteins identified as significantly changing in proteomic experiments, or identified as susceptibility disease genes in genomic studies, can be placed in the context of protein interaction networks in order to assign these genes and proteins to pathways and protein complexes. Genes2Networks is a software system that integrates the content of ten mammalian interaction network datasets. Filtering techniques to prune low-confidence interactions were implemented. Genes2Networks is delivered as a web-based service using AJAX. The system can be used to extract relevant subnetworks created from "seed" lists of human Entrez gene symbols. The output includes a dynamic linkable three color web-based network map, with a statistical analysis report that identifies significant intermediate nodes used to connect the seed list. Genes2Networks is powerful web-based software that can help experimental biologists to interpret lists of genes and proteins such as those commonly produced through genomic and proteomic experiments, as well as lists of genes and proteins associated with disease processes. This system can be used to find relationships between genes and proteins from seed lists, and predict additional genes or proteins that may play key roles in common pathways or protein complexes.

A Scalable Approach for Discovering Conserved Active Subnetworks across Species

PubMed Central

Verfaillie, Catherine M.; Hu, Wei-Shou; Myers, Chad L.

2010-01-01

Overlaying differential changes in gene expression on protein interaction networks has proven to be a useful approach to interpreting the cell's dynamic response to a changing environment. Despite successes in finding active subnetworks in the context of a single species, the idea of overlaying lists of differentially expressed genes on networks has not yet been extended to support the analysis of multiple species' interaction networks. To address this problem, we designed a scalable, cross-species network search algorithm, neXus (Network - cross(X)-species - Search), that discovers conserved, active subnetworks based on parallel differential expression studies in multiple species. Our approach leverages functional linkage networks, which provide more comprehensive coverage of functional relationships than physical interaction networks by combining heterogeneous types of genomic data. We applied our cross-species approach to identify conserved modules that are differentially active in stem cells relative to differentiated cells based on parallel gene expression studies and functional linkage networks from mouse and human. We find hundreds of conserved active subnetworks enriched for stem cell-associated functions such as cell cycle, DNA repair, and chromatin modification processes. Using a variation of this approach, we also find a number of species-specific networks, which likely reflect mechanisms of stem cell function that have diverged between mouse and human. We assess the statistical significance of the subnetworks by comparing them with subnetworks discovered on random permutations of the differential expression data. We also describe several case examples that illustrate the utility of comparative analysis of active subnetworks. PMID:21170309

Talking and Learning Physics: Predicting Future Grades from Network Measures and Force Concept Inventory Pretest Scores

ERIC Educational Resources Information Center

Bruun, Jesper; Brewe, Eric

2013-01-01

The role of student interactions in learning situations is a foundation of sociocultural learning theory, and social network analysis can be used to quantify student relations. We discuss how self-reported student interactions can be viewed as processes of meaning making and use this to understand how quantitative measures that describe the…

Mining for recurrent long-range interactions in RNA structures reveals embedded hierarchies in network families.

PubMed

Reinharz, Vladimir; Soulé, Antoine; Westhof, Eric; Waldispühl, Jérôme; Denise, Alain

2018-05-04

The wealth of the combinatorics of nucleotide base pairs enables RNA molecules to assemble into sophisticated interaction networks, which are used to create complex 3D substructures. These interaction networks are essential to shape the 3D architecture of the molecule, and also to provide the key elements to carry molecular functions such as protein or ligand binding. They are made of organised sets of long-range tertiary interactions which connect distinct secondary structure elements in 3D structures. Here, we present a de novo data-driven approach to extract automatically from large data sets of full RNA 3D structures the recurrent interaction networks (RINs). Our methodology enables us for the first time to detect the interaction networks connecting distinct components of the RNA structure, highlighting their diversity and conservation through non-related functional RNAs. We use a graphical model to perform pairwise comparisons of all RNA structures available and to extract RINs and modules. Our analysis yields a complete catalog of RNA 3D structures available in the Protein Data Bank and reveals the intricate hierarchical organization of the RNA interaction networks and modules. We assembled our results in an online database (http://carnaval.lri.fr) which will be regularly updated. Within the site, a tool allows users with a novel RNA structure to detect automatically whether the novel structure contains previously observed RINs.

PhenomeExpress: a refined network analysis of expression datasets by inclusion of known disease phenotypes.

PubMed

Soul, Jamie; Hardingham, Timothy E; Boot-Handford, Raymond P; Schwartz, Jean-Marc

2015-01-29

We describe a new method, PhenomeExpress, for the analysis of transcriptomic datasets to identify pathogenic disease mechanisms. Our analysis method includes input from both protein-protein interaction and phenotype similarity networks. This introduces valuable information from disease relevant phenotypes, which aids the identification of sub-networks that are significantly enriched in differentially expressed genes and are related to the disease relevant phenotypes. This contrasts with many active sub-network detection methods, which rely solely on protein-protein interaction networks derived from compounded data of many unrelated biological conditions and which are therefore not specific to the context of the experiment. PhenomeExpress thus exploits readily available animal model and human disease phenotype information. It combines this prior evidence of disease phenotypes with the experimentally derived disease data sets to provide a more targeted analysis. Two case studies, in subchondral bone in osteoarthritis and in Pax5 in acute lymphoblastic leukaemia, demonstrate that PhenomeExpress identifies core disease pathways in both mouse and human disease expression datasets derived from different technologies. We also validate the approach by comparison to state-of-the-art active sub-network detection methods, which reveals how it may enhance the detection of molecular phenotypes and provide a more detailed context to those previously identified as possible candidates.

Synaptic activity induces input-specific rearrangements in a targeted synaptic protein interaction network.

PubMed

Lautz, Jonathan D; Brown, Emily A; VanSchoiack, Alison A Williams; Smith, Stephen E P

2018-05-27

Cells utilize dynamic, network level rearrangements in highly interconnected protein interaction networks to transmit and integrate information from distinct signaling inputs. Despite the importance of protein interaction network dynamics, the organizational logic underlying information flow through these networks is not well understood. Previously, we developed the quantitative multiplex co-immunoprecipitation platform, which allows for the simultaneous and quantitative measurement of the amount of co-association between large numbers of proteins in shared complexes. Here, we adapt quantitative multiplex co-immunoprecipitation to define the activity dependent dynamics of an 18-member protein interaction network in order to better understand the underlying principles governing glutamatergic signal transduction. We first establish that immunoprecipitation detected by flow cytometry can detect activity dependent changes in two known protein-protein interactions (Homer1-mGluR5 and PSD-95-SynGAP). We next demonstrate that neuronal stimulation elicits a coordinated change in our targeted protein interaction network, characterized by the initial dissociation of Homer1 and SynGAP-containing complexes followed by increased associations among glutamate receptors and PSD-95. Finally, we show that stimulation of distinct glutamate receptor types results in different modular sets of protein interaction network rearrangements, and that cells activate both modules in order to integrate complex inputs. This analysis demonstrates that cells respond to distinct types of glutamatergic input by modulating different combinations of protein co-associations among a targeted network of proteins. Our data support a model of synaptic plasticity in which synaptic stimulation elicits dissociation of preexisting multiprotein complexes, opening binding slots in scaffold proteins and allowing for the recruitment of additional glutamatergic receptors. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Understanding cancer complexome using networks, spectral graph theory and multilayer framework

NASA Astrophysics Data System (ADS)

Rai, Aparna; Pradhan, Priodyuti; Nagraj, Jyothi; Lohitesh, K.; Chowdhury, Rajdeep; Jalan, Sarika

2017-02-01

Cancer complexome comprises a heterogeneous and multifactorial milieu that varies in cytology, physiology, signaling mechanisms and response to therapy. The combined framework of network theory and spectral graph theory along with the multilayer analysis provides a comprehensive approach to analyze the proteomic data of seven different cancers, namely, breast, oral, ovarian, cervical, lung, colon and prostate. Our analysis demonstrates that the protein-protein interaction networks of the normal and the cancerous tissues associated with the seven cancers have overall similar structural and spectral properties. However, few of these properties implicate unsystematic changes from the normal to the disease networks depicting difference in the interactions and highlighting changes in the complexity of different cancers. Importantly, analysis of common proteins of all the cancer networks reveals few proteins namely the sensors, which not only occupy significant position in all the layers but also have direct involvement in causing cancer. The prediction and analysis of miRNAs targeting these sensor proteins hint towards the possible role of these proteins in tumorigenesis. This novel approach helps in understanding cancer at the fundamental level and provides a clue to develop promising and nascent concept of single drug therapy for multiple diseases as well as personalized medicine.

Understanding cancer complexome using networks, spectral graph theory and multilayer framework.

PubMed

Rai, Aparna; Pradhan, Priodyuti; Nagraj, Jyothi; Lohitesh, K; Chowdhury, Rajdeep; Jalan, Sarika

2017-02-03

Cancer complexome comprises a heterogeneous and multifactorial milieu that varies in cytology, physiology, signaling mechanisms and response to therapy. The combined framework of network theory and spectral graph theory along with the multilayer analysis provides a comprehensive approach to analyze the proteomic data of seven different cancers, namely, breast, oral, ovarian, cervical, lung, colon and prostate. Our analysis demonstrates that the protein-protein interaction networks of the normal and the cancerous tissues associated with the seven cancers have overall similar structural and spectral properties. However, few of these properties implicate unsystematic changes from the normal to the disease networks depicting difference in the interactions and highlighting changes in the complexity of different cancers. Importantly, analysis of common proteins of all the cancer networks reveals few proteins namely the sensors, which not only occupy significant position in all the layers but also have direct involvement in causing cancer. The prediction and analysis of miRNAs targeting these sensor proteins hint towards the possible role of these proteins in tumorigenesis. This novel approach helps in understanding cancer at the fundamental level and provides a clue to develop promising and nascent concept of single drug therapy for multiple diseases as well as personalized medicine.

Network-Induced Classification Kernels for Gene Expression Profile Analysis

PubMed Central

Dror, Gideon; Shamir, Ron

2012-01-01

Abstract Computational classification of gene expression profiles into distinct disease phenotypes has been highly successful to date. Still, robustness, accuracy, and biological interpretation of the results have been limited, and it was suggested that use of protein interaction information jointly with the expression profiles can improve the results. Here, we study three aspects of this problem. First, we show that interactions are indeed relevant by showing that co-expressed genes tend to be closer in the network of interactions. Second, we show that the improved performance of one extant method utilizing expression and interactions is not really due to the biological information in the network, while in another method this is not the case. Finally, we develop a new kernel method—called NICK—that integrates network and expression data for SVM classification, and demonstrate that overall it achieves better results than extant methods while running two orders of magnitude faster. PMID:22697242

Prediction of interface residue based on the features of residue interaction network.

PubMed

Jiao, Xiong; Ranganathan, Shoba

2017-11-07

Protein-protein interaction plays a crucial role in the cellular biological processes. Interface prediction can improve our understanding of the molecular mechanisms of the related processes and functions. In this work, we propose a classification method to recognize the interface residue based on the features of a weighted residue interaction network. The random forest algorithm is used for the prediction and 16 network parameters and the B-factor are acting as the element of the input feature vector. Compared with other similar work, the method is feasible and effective. The relative importance of these features also be analyzed to identify the key feature for the prediction. Some biological meaning of the important feature is explained. The results of this work can be used for the related work about the structure-function relationship analysis via a residue interaction network model. Copyright © 2017 Elsevier Ltd. All rights reserved.

CytoCluster: A Cytoscape Plugin for Cluster Analysis and Visualization of Biological Networks.

PubMed

Li, Min; Li, Dongyan; Tang, Yu; Wu, Fangxiang; Wang, Jianxin

2017-08-31

Nowadays, cluster analysis of biological networks has become one of the most important approaches to identifying functional modules as well as predicting protein complexes and network biomarkers. Furthermore, the visualization of clustering results is crucial to display the structure of biological networks. Here we present CytoCluster, a cytoscape plugin integrating six clustering algorithms, HC-PIN (Hierarchical Clustering algorithm in Protein Interaction Networks), OH-PIN (identifying Overlapping and Hierarchical modules in Protein Interaction Networks), IPCA (Identifying Protein Complex Algorithm), ClusterONE (Clustering with Overlapping Neighborhood Expansion), DCU (Detecting Complexes based on Uncertain graph model), IPC-MCE (Identifying Protein Complexes based on Maximal Complex Extension), and BinGO (the Biological networks Gene Ontology) function. Users can select different clustering algorithms according to their requirements. The main function of these six clustering algorithms is to detect protein complexes or functional modules. In addition, BinGO is used to determine which Gene Ontology (GO) categories are statistically overrepresented in a set of genes or a subgraph of a biological network. CytoCluster can be easily expanded, so that more clustering algorithms and functions can be added to this plugin. Since it was created in July 2013, CytoCluster has been downloaded more than 9700 times in the Cytoscape App store and has already been applied to the analysis of different biological networks. CytoCluster is available from http://apps.cytoscape.org/apps/cytocluster.

CytoCluster: A Cytoscape Plugin for Cluster Analysis and Visualization of Biological Networks

PubMed Central

Li, Min; Li, Dongyan; Tang, Yu; Wang, Jianxin

2017-01-01

Nowadays, cluster analysis of biological networks has become one of the most important approaches to identifying functional modules as well as predicting protein complexes and network biomarkers. Furthermore, the visualization of clustering results is crucial to display the structure of biological networks. Here we present CytoCluster, a cytoscape plugin integrating six clustering algorithms, HC-PIN (Hierarchical Clustering algorithm in Protein Interaction Networks), OH-PIN (identifying Overlapping and Hierarchical modules in Protein Interaction Networks), IPCA (Identifying Protein Complex Algorithm), ClusterONE (Clustering with Overlapping Neighborhood Expansion), DCU (Detecting Complexes based on Uncertain graph model), IPC-MCE (Identifying Protein Complexes based on Maximal Complex Extension), and BinGO (the Biological networks Gene Ontology) function. Users can select different clustering algorithms according to their requirements. The main function of these six clustering algorithms is to detect protein complexes or functional modules. In addition, BinGO is used to determine which Gene Ontology (GO) categories are statistically overrepresented in a set of genes or a subgraph of a biological network. CytoCluster can be easily expanded, so that more clustering algorithms and functions can be added to this plugin. Since it was created in July 2013, CytoCluster has been downloaded more than 9700 times in the Cytoscape App store and has already been applied to the analysis of different biological networks. CytoCluster is available from http://apps.cytoscape.org/apps/cytocluster. PMID:28858211

Assessing the utility of gene co-expression stability in combination with correlation in the analysis of protein-protein interaction networks

PubMed Central

2011-01-01

Background Gene co-expression, in the form of a correlation coefficient, has been valuable in the analysis, classification and prediction of protein-protein interactions. However, it is susceptible to bias from a few samples having a large effect on the correlation coefficient. Gene co-expression stability is a means of quantifying this bias, with high stability indicating robust, unbiased co-expression correlation coefficients. We assess the utility of gene co-expression stability as an additional measure to support the co-expression correlation in the analysis of protein-protein interaction networks. Results We studied the patterns of co-expression correlation and stability in interacting proteins with respect to their interaction promiscuity, levels of intrinsic disorder, and essentiality or disease-relatedness. Co-expression stability, along with co-expression correlation, acts as a better classifier of hub proteins in interaction networks, than co-expression correlation alone, enabling the identification of a class of hubs that are functionally distinct from the widely accepted transient (date) and obligate (party) hubs. Proteins with high levels of intrinsic disorder have low co-expression correlation and high stability with their interaction partners suggesting their involvement in transient interactions, except for a small group that have high co-expression correlation and are typically subunits of stable complexes. Similar behavior was seen for disease-related and essential genes. Interacting proteins that are both disordered have higher co-expression stability than ordered protein pairs. Using co-expression correlation and stability, we found that transient interactions are more likely to occur between an ordered and a disordered protein while obligate interactions primarily occur between proteins that are either both ordered, or disordered. Conclusions We observe that co-expression stability shows distinct patterns in structurally and functionally different groups of proteins and interactions. We conclude that it is a useful and important measure to be used in concert with gene co-expression correlation for further insights into the characteristics of proteins in the context of their interaction network. PMID:22369639

Quantification of Interactions between Dynamic Cellular Network Functionalities by Cascaded Layering

PubMed Central

Prescott, Thomas P.; Lang, Moritz; Papachristodoulou, Antonis

2015-01-01

Large, naturally evolved biomolecular networks typically fulfil multiple functions. When modelling or redesigning such systems, functional subsystems are often analysed independently first, before subsequent integration into larger-scale computational models. In the design and analysis process, it is therefore important to quantitatively analyse and predict the dynamics of the interactions between integrated subsystems; in particular, how the incremental effect of integrating a subsystem into a network depends on the existing dynamics of that network. In this paper we present a framework for simulating the contribution of any given functional subsystem when integrated together with one or more other subsystems. This is achieved through a cascaded layering of a network into functional subsystems, where each layer is defined by an appropriate subset of the reactions. We exploit symmetries in our formulation to exhaustively quantify each subsystem’s incremental effects with minimal computational effort. When combining subsystems, their isolated behaviour may be amplified, attenuated, or be subject to more complicated effects. We propose the concept of mutual dynamics to quantify such nonlinear phenomena, thereby defining the incompatibility and cooperativity between all pairs of subsystems when integrated into any larger network. We exemplify our theoretical framework by analysing diverse behaviours in three dynamic models of signalling and metabolic pathways: the effect of crosstalk mechanisms on the dynamics of parallel signal transduction pathways; reciprocal side-effects between several integral feedback mechanisms and the subsystems they stabilise; and consequences of nonlinear interactions between elementary flux modes in glycolysis for metabolic engineering strategies. Our analysis shows that it is not sufficient to just specify subsystems and analyse their pairwise interactions; the environment in which the interaction takes place must also be explicitly defined. Our framework provides a natural representation of nonlinear interaction phenomena, and will therefore be an important tool for modelling large-scale evolved or synthetic biomolecular networks. PMID:25933116

Allosteric Regulation of the Hsp90 Dynamics and Stability by Client Recruiter Cochaperones: Protein Structure Network Modeling

PubMed Central

Blacklock, Kristin; Verkhivker, Gennady M.

2014-01-01

The fundamental role of the Hsp90 chaperone in supporting functional activity of diverse protein clients is anchored by specific cochaperones. A family of immune sensing client proteins is delivered to the Hsp90 system with the aid of cochaperones Sgt1 and Rar1 that act cooperatively with Hsp90 to form allosterically regulated dynamic complexes. In this work, functional dynamics and protein structure network modeling are combined to dissect molecular mechanisms of Hsp90 regulation by the client recruiter cochaperones. Dynamic signatures of the Hsp90-cochaperone complexes are manifested in differential modulation of the conformational mobility in the Hsp90 lid motif. Consistent with the experiments, we have determined that targeted reorganization of the lid dynamics is a unifying characteristic of the client recruiter cochaperones. Protein network analysis of the essential conformational space of the Hsp90-cochaperone motions has identified structurally stable interaction communities, interfacial hubs and key mediating residues of allosteric communication pathways that act concertedly with the shifts in conformational equilibrium. The results have shown that client recruiter cochaperones can orchestrate global changes in the dynamics and stability of the interaction networks that could enhance the ATPase activity and assist in the client recruitment. The network analysis has recapitulated a broad range of structural and mutagenesis experiments, particularly clarifying the elusive role of Rar1 as a regulator of the Hsp90 interactions and a stability enhancer of the Hsp90-cochaperone complexes. Small-world organization of the interaction networks in the Hsp90 regulatory complexes gives rise to a strong correspondence between highly connected local interfacial hubs, global mediator residues of allosteric interactions and key functional hot spots of the Hsp90 activity. We have found that cochaperone-induced conformational changes in Hsp90 may be determined by specific interaction networks that can inhibit or promote progression of the ATPase cycle and thus control the recruitment of client proteins. PMID:24466147

Allosteric regulation of the Hsp90 dynamics and stability by client recruiter cochaperones: protein structure network modeling.

PubMed

Blacklock, Kristin; Verkhivker, Gennady M

2014-01-01

The fundamental role of the Hsp90 chaperone in supporting functional activity of diverse protein clients is anchored by specific cochaperones. A family of immune sensing client proteins is delivered to the Hsp90 system with the aid of cochaperones Sgt1 and Rar1 that act cooperatively with Hsp90 to form allosterically regulated dynamic complexes. In this work, functional dynamics and protein structure network modeling are combined to dissect molecular mechanisms of Hsp90 regulation by the client recruiter cochaperones. Dynamic signatures of the Hsp90-cochaperone complexes are manifested in differential modulation of the conformational mobility in the Hsp90 lid motif. Consistent with the experiments, we have determined that targeted reorganization of the lid dynamics is a unifying characteristic of the client recruiter cochaperones. Protein network analysis of the essential conformational space of the Hsp90-cochaperone motions has identified structurally stable interaction communities, interfacial hubs and key mediating residues of allosteric communication pathways that act concertedly with the shifts in conformational equilibrium. The results have shown that client recruiter cochaperones can orchestrate global changes in the dynamics and stability of the interaction networks that could enhance the ATPase activity and assist in the client recruitment. The network analysis has recapitulated a broad range of structural and mutagenesis experiments, particularly clarifying the elusive role of Rar1 as a regulator of the Hsp90 interactions and a stability enhancer of the Hsp90-cochaperone complexes. Small-world organization of the interaction networks in the Hsp90 regulatory complexes gives rise to a strong correspondence between highly connected local interfacial hubs, global mediator residues of allosteric interactions and key functional hot spots of the Hsp90 activity. We have found that cochaperone-induced conformational changes in Hsp90 may be determined by specific interaction networks that can inhibit or promote progression of the ATPase cycle and thus control the recruitment of client proteins.

Convergence analysis of directed signed networks via an M-matrix approach

NASA Astrophysics Data System (ADS)

Meng, Deyuan

2018-04-01

This paper aims at solving convergence problems on directed signed networks with multiple nodes, where interactions among nodes are described by signed digraphs. The convergence analysis is achieved by matrix-theoretic and graph-theoretic tools, in which M-matrices play a central role. The fundamental digon sign-symmetry assumption upon signed digraphs can be removed with the proposed analysis approach. Furthermore, necessary and sufficient conditions are established for semi-positive and positive stabilities of Laplacian matrices of signed digraphs, respectively. A benefit of this result is that given strong connectivity, a directed signed network can achieve bipartite consensus (or state stability) if and only if the signed digraph associated with it is structurally balanced (or unbalanced). If the interactions between nodes are described by a signed digraph only with spanning trees, a directed signed network can achieve interval bipartite consensus (or state stability) if and only if the signed digraph contains a structurally balanced (or unbalanced) rooted subgraph. Simulations are given to illustrate the developed results by considering signed networks associated with digon sign-unsymmetric signed digraphs.

Network-Based Methods for Identifying Key Active Proteins in the Extracellular Electron Transfer Process in Shewanella oneidensis MR-1.

PubMed

Ding, Dewu; Sun, Xiao

2018-01-16

Shewanella oneidensis MR-1 can transfer electrons from the intracellular environment to the extracellular space of the cells to reduce the extracellular insoluble electron acceptors (Extracellular Electron Transfer, EET). Benefiting from this EET capability, Shewanella has been widely used in different areas, such as energy production, wastewater treatment, and bioremediation. Genome-wide proteomics data was used to determine the active proteins involved in activating the EET process. We identified 1012 proteins with decreased expression and 811 proteins with increased expression when the EET process changed from inactivation to activation. We then networked these proteins to construct the active protein networks, and identified the top 20 key active proteins by network centralization analysis, including metabolism- and energy-related proteins, signal and transcriptional regulatory proteins, translation-related proteins, and the EET-related proteins. We also constructed the integrated protein interaction and transcriptional regulatory networks for the active proteins, then found three exclusive active network motifs involved in activating the EET process-Bi-feedforward Loop, Regulatory Cascade with a Feedback, and Feedback with a Protein-Protein Interaction (PPI)-and identified the active proteins involved in these motifs. Both enrichment analysis and comparative analysis to the whole-genome data implicated the multiheme c -type cytochromes and multiple signal processing proteins involved in the process. Furthermore, the interactions of these motif-guided active proteins and the involved functional modules were discussed. Collectively, by using network-based methods, this work reported a proteome-wide search for the key active proteins that potentially activate the EET process.

Gene regulation is governed by a core network in hepatocellular carcinoma.

PubMed

Gu, Zuguang; Zhang, Chenyu; Wang, Jin

2012-05-01

Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide, and the mechanisms that lead to the disease are still relatively unclear. However, with the development of high-throughput technologies it is possible to gain a systematic view of biological systems to enhance the understanding of the roles of genes associated with HCC. Thus, analysis of the mechanism of molecule interactions in the context of gene regulatory networks can reveal specific sub-networks that lead to the development of HCC. In this study, we aimed to identify the most important gene regulations that are dysfunctional in HCC generation. Our method for constructing gene regulatory network is based on predicted target interactions, experimentally-supported interactions, and co-expression model. Regulators in the network included both transcription factors and microRNAs to provide a complete view of gene regulation. Analysis of gene regulatory network revealed that gene regulation in HCC is highly modular, in which different sets of regulators take charge of specific biological processes. We found that microRNAs mainly control biological functions related to mitochondria and oxidative reduction, while transcription factors control immune responses, extracellular activity and the cell cycle. On the higher level of gene regulation, there exists a core network that organizes regulations between different modules and maintains the robustness of the whole network. There is direct experimental evidence for most of the regulators in the core gene regulatory network relating to HCC. We infer it is the central controller of gene regulation. Finally, we explored the influence of the core gene regulatory network on biological pathways. Our analysis provides insights into the mechanism of transcriptional and post-transcriptional control in HCC. In particular, we highlight the importance of the core gene regulatory network; we propose that it is highly related to HCC and we believe further experimental validation is worthwhile.

A Social Network Approach to Understanding an Insurgency

DTIC Science & Technology

2007-07-01

and a framework for testing theories regarding struc- tured social relationships.6 Equally relevant is the understanding of a social network approach...A Social Network Approach to Understanding an Insurgency BRIAN REED The study of networks, interactions, and relationships has a long history...characteristics of social network analysis is often counter-intuitive to traditional military thinking, rooted in the efficiency of a hierarchy that

The neural basis of hand gesture comprehension: A meta-analysis of functional magnetic resonance imaging studies.

PubMed

Yang, Jie; Andric, Michael; Mathew, Mili M

2015-10-01

Gestures play an important role in face-to-face communication and have been increasingly studied via functional magnetic resonance imaging. Although a large amount of data has been provided to describe the neural substrates of gesture comprehension, these findings have never been quantitatively summarized and the conclusion is still unclear. This activation likelihood estimation meta-analysis investigated the brain networks underpinning gesture comprehension while considering the impact of gesture type (co-speech gestures vs. speech-independent gestures) and task demand (implicit vs. explicit) on the brain activation of gesture comprehension. The meta-analysis of 31 papers showed that as hand actions, gestures involve a perceptual-motor network important for action recognition. As meaningful symbols, gestures involve a semantic network for conceptual processing. Finally, during face-to-face interactions, gestures involve a network for social emotive processes. Our finding also indicated that gesture type and task demand influence the involvement of the brain networks during gesture comprehension. The results highlight the complexity of gesture comprehension, and suggest that future research is necessary to clarify the dynamic interactions among these networks. Copyright © 2015 Elsevier Ltd. All rights reserved.

Topological and organizational properties of the products of house-keeping and tissue-specific genes in protein-protein interaction networks.

PubMed

Lin, Wen-Hsien; Liu, Wei-Chung; Hwang, Ming-Jing

2009-03-11

Human cells of various tissue types differ greatly in morphology despite having the same set of genetic information. Some genes are expressed in all cell types to perform house-keeping functions, while some are selectively expressed to perform tissue-specific functions. In this study, we wished to elucidate how proteins encoded by human house-keeping genes and tissue-specific genes are organized in human protein-protein interaction networks. We constructed protein-protein interaction networks for different tissue types using two gene expression datasets and one protein-protein interaction database. We then calculated three network indices of topological importance, the degree, closeness, and betweenness centralities, to measure the network position of proteins encoded by house-keeping and tissue-specific genes, and quantified their local connectivity structure. Compared to a random selection of proteins, house-keeping gene-encoded proteins tended to have a greater number of directly interacting neighbors and occupy network positions in several shortest paths of interaction between protein pairs, whereas tissue-specific gene-encoded proteins did not. In addition, house-keeping gene-encoded proteins tended to connect with other house-keeping gene-encoded proteins in all tissue types, whereas tissue-specific gene-encoded proteins also tended to connect with other tissue-specific gene-encoded proteins, but only in approximately half of the tissue types examined. Our analysis showed that house-keeping gene-encoded proteins tend to occupy important network positions, while those encoded by tissue-specific genes do not. The biological implications of our findings were discussed and we proposed a hypothesis regarding how cells organize their protein tools in protein-protein interaction networks. Our results led us to speculate that house-keeping gene-encoded proteins might form a core in human protein-protein interaction networks, while clusters of tissue-specific gene-encoded proteins are attached to the core at more peripheral positions of the networks.

Unified Approach to Modeling and Simulation of Space Communication Networks and Systems

NASA Technical Reports Server (NTRS)

Barritt, Brian; Bhasin, Kul; Eddy, Wesley; Matthews, Seth

2010-01-01

Network simulator software tools are often used to model the behaviors and interactions of applications, protocols, packets, and data links in terrestrial communication networks. Other software tools that model the physics, orbital dynamics, and RF characteristics of space systems have matured to allow for rapid, detailed analysis of space communication links. However, the absence of a unified toolset that integrates the two modeling approaches has encumbered the systems engineers tasked with the design, architecture, and analysis of complex space communication networks and systems. This paper presents the unified approach and describes the motivation, challenges, and our solution - the customization of the network simulator to integrate with astronautical analysis software tools for high-fidelity end-to-end simulation. Keywords space; communication; systems; networking; simulation; modeling; QualNet; STK; integration; space networks

Synchronization within, and interactions between, the default mode and dorsal attention networks in relapsing-remitting multiple sclerosis.

PubMed

Huang, Muhua; Zhou, Fuqing; Wu, Lin; Wang, Bo; Wan, Hui; Li, Fangjun; Zeng, Xianjun; Gong, Honghan

2018-01-01

The effects of the interactions between the default mode network (DMN) and the dorsal attention network (DAN), which present anticorrelated behaviors, in relapsing-remitting multiple sclerosis (RRMS) are poorly understood. This study used resting-state functional connectivity (FC) and the Granger causality test (GCT) to examine changes in the undirected and effective functional network connectivity (FNC) between the two networks during the remitting phase in RRMS patients. Thirty-three patients experiencing a clinically diagnosed remitting phase of RRMS and 33 well-matched healthy control subjects participated in this study. First, an independent component (IC) analysis was performed to preprocess the functional magnetic resonance imaging data and select resting-state networks. Then, an FNC analysis and the GCT were combined to examine the temporal correlations between the ICs of the DMN and DAN and to identify correlations with clinical markers. Compared with the healthy subjects, the RRMS patients in the remitting phase showed the following: 1) significantly decreased FC within the DAN in the postcentral gyrus and decreased FC within the DMN in several regions except the parahippocampal gyrus, where increased FC was observed; 2) a relatively stable interaction between the two anticorrelated networks as well as a driving connectivity from the DAN to DMN (IC15); and 3) significantly positive correlations between the connectivity coefficient of the right superior temporal gyrus and the Modified Fatigue Impact Scale score ( ρ = 0.379, p = 0.036). Adaptive mechanisms that maintain stable interactions might occur between the DMN and DAN during the remitting phase in RRMS patients.

Systematic analysis of Ca2+ homeostasis in Saccharomyces cerevisiae based on chemical-genetic interaction profiles

PubMed Central

Ghanegolmohammadi, Farzan; Yoshida, Mitsunori; Ohnuki, Shinsuke; Sukegawa, Yuko; Okada, Hiroki; Obara, Keisuke; Kihara, Akio; Suzuki, Kuninori; Kojima, Tetsuya; Yachie, Nozomu; Hirata, Dai; Ohya, Yoshikazu

2017-01-01

We investigated the global landscape of Ca2+ homeostasis in budding yeast based on high-dimensional chemical-genetic interaction profiles. The morphological responses of 62 Ca2+-sensitive (cls) mutants were quantitatively analyzed with the image processing program CalMorph after exposure to a high concentration of Ca2+. After a generalized linear model was applied, an analysis of covariance model was used to detect significant Ca2+–cls interactions. We found that high-dimensional, morphological Ca2+–cls interactions were mixed with positive (86%) and negative (14%) chemical-genetic interactions, whereas one-dimensional fitness Ca2+–cls interactions were all negative in principle. Clustering analysis with the interaction profiles revealed nine distinct gene groups, six of which were functionally associated. In addition, characterization of Ca2+–cls interactions revealed that morphology-based negative interactions are unique signatures of sensitized cellular processes and pathways. Principal component analysis was used to discriminate between suppression and enhancement of the Ca2+-sensitive phenotypes triggered by inactivation of calcineurin, a Ca2+-dependent phosphatase. Finally, similarity of the interaction profiles was used to reveal a connected network among the Ca2+ homeostasis units acting in different cellular compartments. Our analyses of high-dimensional chemical-genetic interaction profiles provide novel insights into the intracellular network of yeast Ca2+ homeostasis. PMID:28566553

A Strategy Based on Protein-Protein Interface Motifs May Help in Identifying Drug Off-Targets

PubMed Central

Engin, H. Billur; Keskin, Ozlem; Nussinov, Ruth; Gursoy, Attila

2014-01-01

Networks are increasingly used to study the impact of drugs at the systems level. From the algorithmic standpoint, a drug can ‘attack’ nodes or edges of a protein-protein interaction network. In this work, we propose a new network strategy, “The Interface Attack”, based on protein-protein interfaces. Similar interface architectures can occur between unrelated proteins. Consequently, in principle, a drug that binds to one has a certain probability of binding others. The interface attack strategy simultaneously removes from the network all interactions that consist of similar interface motifs. This strategy is inspired by network pharmacology and allows inferring potential off-targets. We introduce a network model which we call “Protein Interface and Interaction Network (P2IN)”, which is the integration of protein-protein interface structures and protein interaction networks. This interface-based network organization clarifies which protein pairs have structurally similar interfaces, and which proteins may compete to bind the same surface region. We built the P2IN of p53 signaling network and performed network robustness analysis. We show that (1) ‘hitting’ frequent interfaces (a set of edges distributed around the network) might be as destructive as eleminating high degree proteins (hub nodes); (2) frequent interfaces are not always topologically critical elements in the network; and (3) interface attack may reveal functional changes in the system better than attack of single proteins. In the off-target detection case study, we found that drugs blocking the interface between CDK6 and CDKN2D may also affect the interaction between CDK4 and CDKN2D. PMID:22817115

Measurement and visualization of face-to-face interaction among community-dwelling older adults using wearable sensors.

PubMed

Masumoto, Kouhei; Yaguchi, Takaharu; Matsuda, Hiroshi; Tani, Hideaki; Tozuka, Keisuke; Kondo, Narihiko; Okada, Shuichi

2017-10-01

A number of interventions have been undertaken to develop and promote social networks among community-dwelling older adults. However, it has been difficult to examine the effects of these interventions, because of problems in assessing interactions. The present study was designed to quantitatively measure and visualize face-to-face interactions among elderly participants in an exercise program. We also examined relationships among interactional variables, personality and interest in community involvement, including interactions with the local community. Older adults living in the same community were recruited to participate in an exercise program that consisted of four sessions. We collected data on face-to-face interactions of the participants by using a wearable sensor technology device. Network analysis identified the communication networks of participants in the exercise program, as well as changes in these networks. Additionally, there were significant correlations between the number of people involved in face-to-face interactions and changes in both interest in community involvement and interactions with local community residents, as well as personality traits, including agreeableness. Social networks in the community are essential for solving problems caused by the aging society. We showed the possible applications of face-to-face interactional data for identifying core participants having many interactions, and isolated participants having only a few interactions within the community. Such data would be useful for carrying out efficient interventions for increasing participants' involvement with their community. Geriatr Gerontol Int 2017; 17: 1752-1758. © 2017 Japan Geriatrics Society.

Characterizing Social Interaction in Tobacco-Oriented Social Networks: An Empirical Analysis.

PubMed

Liang, Yunji; Zheng, Xiaolong; Zeng, Daniel Dajun; Zhou, Xingshe; Leischow, Scott James; Chung, Wingyan

2015-06-19

Social media is becoming a new battlefield for tobacco "wars". Evaluating the current situation is very crucial for the advocacy of tobacco control in the age of social media. To reveal the impact of tobacco-related user-generated content, this paper characterizes user interaction and social influence utilizing social network analysis and information theoretic approaches. Our empirical studies demonstrate that the exploding pro-tobacco content has long-lasting effects with more active users and broader influence, and reveal the shortage of social media resources in global tobacco control. It is found that the user interaction in the pro-tobacco group is more active, and user-generated content for tobacco promotion is more successful in obtaining user attention. Furthermore, we construct three tobacco-related social networks and investigate the topological patterns of these tobacco-related social networks. We find that the size of the pro-tobacco network overwhelms the others, which suggests a huge number of users are exposed to the pro-tobacco content. These results indicate that the gap between tobacco promotion and tobacco control is widening and tobacco control may be losing ground to tobacco promotion in social media.

Characterizing Social Interaction in Tobacco-Oriented Social Networks: An Empirical Analysis

PubMed Central

Liang, Yunji; Zheng, Xiaolong; Zeng, Daniel Dajun; Zhou, Xingshe; Leischow, Scott James; Chung, Wingyan

2015-01-01

Social media is becoming a new battlefield for tobacco “wars”. Evaluating the current situation is very crucial for the advocacy of tobacco control in the age of social media. To reveal the impact of tobacco-related user-generated content, this paper characterizes user interaction and social influence utilizing social network analysis and information theoretic approaches. Our empirical studies demonstrate that the exploding pro-tobacco content has long-lasting effects with more active users and broader influence, and reveal the shortage of social media resources in global tobacco control. It is found that the user interaction in the pro-tobacco group is more active, and user-generated content for tobacco promotion is more successful in obtaining user attention. Furthermore, we construct three tobacco-related social networks and investigate the topological patterns of these tobacco-related social networks. We find that the size of the pro-tobacco network overwhelms the others, which suggests a huge number of users are exposed to the pro-tobacco content. These results indicate that the gap between tobacco promotion and tobacco control is widening and tobacco control may be losing ground to tobacco promotion in social media. PMID:26091553

Molecular dynamics simulations and structure-based network analysis reveal structural and functional aspects of G-protein coupled receptor dimer interactions.

PubMed

Baltoumas, Fotis A; Theodoropoulou, Margarita C; Hamodrakas, Stavros J

2016-06-01

A significant amount of experimental evidence suggests that G-protein coupled receptors (GPCRs) do not act exclusively as monomers but also form biologically relevant dimers and oligomers. However, the structural determinants, stoichiometry and functional importance of GPCR oligomerization remain topics of intense speculation. In this study we attempted to evaluate the nature and dynamics of GPCR oligomeric interactions. A representative set of GPCR homodimers were studied through Coarse-Grained Molecular Dynamics simulations, combined with interface analysis and concepts from network theory for the construction and analysis of dynamic structural networks. Our results highlight important structural determinants that seem to govern receptor dimer interactions. A conserved dynamic behavior was observed among different GPCRs, including receptors belonging in different GPCR classes. Specific GPCR regions were highlighted as the core of the interfaces. Finally, correlations of motion were observed between parts of the dimer interface and GPCR segments participating in ligand binding and receptor activation, suggesting the existence of mechanisms through which dimer formation may affect GPCR function. The results of this study can be used to drive experiments aimed at exploring GPCR oligomerization, as well as in the study of transmembrane protein-protein interactions in general.

Molecular dynamics simulations and structure-based network analysis reveal structural and functional aspects of G-protein coupled receptor dimer interactions

NASA Astrophysics Data System (ADS)

Baltoumas, Fotis A.; Theodoropoulou, Margarita C.; Hamodrakas, Stavros J.

2016-06-01

A significant amount of experimental evidence suggests that G-protein coupled receptors (GPCRs) do not act exclusively as monomers but also form biologically relevant dimers and oligomers. However, the structural determinants, stoichiometry and functional importance of GPCR oligomerization remain topics of intense speculation. In this study we attempted to evaluate the nature and dynamics of GPCR oligomeric interactions. A representative set of GPCR homodimers were studied through Coarse-Grained Molecular Dynamics simulations, combined with interface analysis and concepts from network theory for the construction and analysis of dynamic structural networks. Our results highlight important structural determinants that seem to govern receptor dimer interactions. A conserved dynamic behavior was observed among different GPCRs, including receptors belonging in different GPCR classes. Specific GPCR regions were highlighted as the core of the interfaces. Finally, correlations of motion were observed between parts of the dimer interface and GPCR segments participating in ligand binding and receptor activation, suggesting the existence of mechanisms through which dimer formation may affect GPCR function. The results of this study can be used to drive experiments aimed at exploring GPCR oligomerization, as well as in the study of transmembrane protein-protein interactions in general.

Dynamic Neural Networks Supporting Memory Retrieval

PubMed Central

St. Jacques, Peggy L.; Kragel, Philip A.; Rubin, David C.

2011-01-01

How do separate neural networks interact to support complex cognitive processes such as remembrance of the personal past? Autobiographical memory (AM) retrieval recruits a consistent pattern of activation that potentially comprises multiple neural networks. However, it is unclear how such large-scale neural networks interact and are modulated by properties of the memory retrieval process. In the present functional MRI (fMRI) study, we combined independent component analysis (ICA) and dynamic causal modeling (DCM) to understand the neural networks supporting AM retrieval. ICA revealed four task-related components consistent with the previous literature: 1) Medial Prefrontal Cortex (PFC) Network, associated with self-referential processes, 2) Medial Temporal Lobe (MTL) Network, associated with memory, 3) Frontoparietal Network, associated with strategic search, and 4) Cingulooperculum Network, associated with goal maintenance. DCM analysis revealed that the medial PFC network drove activation within the system, consistent with the importance of this network to AM retrieval. Additionally, memory accessibility and recollection uniquely altered connectivity between these neural networks. Recollection modulated the influence of the medial PFC on the MTL network during elaboration, suggesting that greater connectivity among subsystems of the default network supports greater re-experience. In contrast, memory accessibility modulated the influence of frontoparietal and MTL networks on the medial PFC network, suggesting that ease of retrieval involves greater fluency among the multiple networks contributing to AM. These results show the integration between neural networks supporting AM retrieval and the modulation of network connectivity by behavior. PMID:21550407

Synergistic interactions promote behavior spreading and alter phase transitions on multiplex networks

NASA Astrophysics Data System (ADS)

Liu, Quan-Hui; Wang, Wei; Cai, Shi-Min; Tang, Ming; Lai, Ying-Cheng

2018-02-01

Synergistic interactions are ubiquitous in the real world. Recent studies have revealed that, for a single-layer network, synergy can enhance spreading and even induce an explosive contagion. There is at the present a growing interest in behavior spreading dynamics on multiplex networks. What is the role of synergistic interactions in behavior spreading in such networked systems? To address this question, we articulate a synergistic behavior spreading model on a double layer network, where the key manifestation of the synergistic interactions is that the adoption of one behavior by a node in one layer enhances its probability of adopting the behavior in the other layer. A general result is that synergistic interactions can greatly enhance the spreading of the behaviors in both layers. A remarkable phenomenon is that the interactions can alter the nature of the phase transition associated with behavior adoption or spreading dynamics. In particular, depending on the transmission rate of one behavior in a network layer, synergistic interactions can lead to a discontinuous (first-order) or a continuous (second-order) transition in the adoption scope of the other behavior with respect to its transmission rate. A surprising two-stage spreading process can arise: due to synergy, nodes having adopted one behavior in one layer adopt the other behavior in the other layer and then prompt the remaining nodes in this layer to quickly adopt the behavior. Analytically, we develop an edge-based compartmental theory and perform a bifurcation analysis to fully understand, in the weak synergistic interaction regime where the dynamical correlation between the network layers is negligible, the role of the interactions in promoting the social behavioral spreading dynamics in the whole system.

Social Network Analysis as a Methodological Approach to Explore Health Systems: A Case Study Exploring Support among Senior Managers/Executives in a Hospital Network.

PubMed

De Brún, Aoife; McAuliffe, Eilish

2018-03-13

Health systems research recognizes the complexity of healthcare, and the interacting and interdependent nature of components of a health system. To better understand such systems, innovative methods are required to depict and analyze their structures. This paper describes social network analysis as a methodology to depict, diagnose, and evaluate health systems and networks therein. Social network analysis is a set of techniques to map, measure, and analyze social relationships between people, teams, and organizations. Through use of a case study exploring support relationships among senior managers in a newly established hospital group, this paper illustrates some of the commonly used network- and node-level metrics in social network analysis, and demonstrates the value of these maps and metrics to understand systems. Network analysis offers a valuable approach to health systems and services researchers as it offers a means to depict activity relevant to network questions of interest, to identify opinion leaders, influencers, clusters in the network, and those individuals serving as bridgers across clusters. The strengths and limitations inherent in the method are discussed, and the applications of social network analysis in health services research are explored.

Ontology-based literature mining of E. coli vaccine-associated gene interaction networks.

PubMed

Hur, Junguk; Özgür, Arzucan; He, Yongqun

2017-03-14

Pathogenic Escherichia coli infections cause various diseases in humans and many animal species. However, with extensive E. coli vaccine research, we are still unable to fully protect ourselves against E. coli infections. To more rational development of effective and safe E. coli vaccine, it is important to better understand E. coli vaccine-associated gene interaction networks. In this study, we first extended the Vaccine Ontology (VO) to semantically represent various E. coli vaccines and genes used in the vaccine development. We also normalized E. coli gene names compiled from the annotations of various E. coli strains using a pan-genome-based annotation strategy. The Interaction Network Ontology (INO) includes a hierarchy of various interaction-related keywords useful for literature mining. Using VO, INO, and normalized E. coli gene names, we applied an ontology-based SciMiner literature mining strategy to mine all PubMed abstracts and retrieve E. coli vaccine-associated E. coli gene interactions. Four centrality metrics (i.e., degree, eigenvector, closeness, and betweenness) were calculated for identifying highly ranked genes and interaction types. Using vaccine-related PubMed abstracts, our study identified 11,350 sentences that contain 88 unique INO interactions types and 1,781 unique E. coli genes. Each sentence contained at least one interaction type and two unique E. coli genes. An E. coli gene interaction network of genes and INO interaction types was created. From this big network, a sub-network consisting of 5 E. coli vaccine genes, including carA, carB, fimH, fepA, and vat, and 62 other E. coli genes, and 25 INO interaction types was identified. While many interaction types represent direct interactions between two indicated genes, our study has also shown that many of these retrieved interaction types are indirect in that the two genes participated in the specified interaction process in a required but indirect process. Our centrality analysis of these gene interaction networks identified top ranked E. coli genes and 6 INO interaction types (e.g., regulation and gene expression). Vaccine-related E. coli gene-gene interaction network was constructed using ontology-based literature mining strategy, which identified important E. coli vaccine genes and their interactions with other genes through specific interaction types.

Comparative analysis of protein interactome networks prioritizes candidate genes with cancer signatures.

PubMed

Li, Yongsheng; Sahni, Nidhi; Yi, Song

2016-11-29

Comprehensive understanding of human cancer mechanisms requires the identification of a thorough list of cancer-associated genes, which could serve as biomarkers for diagnoses and therapies in various types of cancer. Although substantial progress has been made in functional studies to uncover genes involved in cancer, these efforts are often time-consuming and costly. Therefore, it remains challenging to comprehensively identify cancer candidate genes. Network-based methods have accelerated this process through the analysis of complex molecular interactions in the cell. However, the extent to which various interactome networks can contribute to prediction of candidate genes responsible for cancer is still enigmatic. In this study, we evaluated different human protein-protein interactome networks and compared their application to cancer gene prioritization. Our results indicate that network analyses can increase the power to identify novel cancer genes. In particular, such predictive power can be enhanced with the use of unbiased systematic protein interaction maps for cancer gene prioritization. Functional analysis reveals that the top ranked genes from network predictions co-occur often with cancer-related terms in literature, and further, these candidate genes are indeed frequently mutated across cancers. Finally, our study suggests that integrating interactome networks with other omics datasets could provide novel insights into cancer-associated genes and underlying molecular mechanisms.

Analysis and Visualization of Internet QA Bulletin Boards Represented as Heterogeneous Networks

NASA Astrophysics Data System (ADS)

Murata, Tsuyoshi; Ikeya, Tomoyuki

Visualizing and analyzing social interactions of CGM (Consumer Generated Media) are important for understanding overall activities on the internet. Social interactions are often represented as simple networks that are composed of homogeneous nodes and edges between them. However, related entities in real world are often not homogeneous. Such relations are naturally represented as heterogeneous networks composed of more than one kind of nodes and edges connecting them. In the case of CGM, for example, users and their contents constitute nodes of heterogeneous networks. There are related users (user communities) and related contents (contents communities) in the heterogeneous networks. Discovering both communities and finding correspondence among them will clarify the characteristics of the communites. This paper describes an attempt for visualizing and analyzing social interactions of Yahoo! Chiebukuro (Japanese Yahoo! Answers). New criteria for measuring correspondence between user communities and board communites are defined, and characteristics of both communities are analyzed using the criteria.

Transfer of Training: Adding Insight through Social Network Analysis

ERIC Educational Resources Information Center

Van den Bossche, Piet; Segers, Mien

2013-01-01

This article reviews studies which apply a social network perspective to examine transfer of training. The theory behind social networks focuses on the interpersonal mechanisms and social structures that exist among interacting units such as people within an organization. A premise of this perspective is that individual's behaviors and outcomes…

Getting "Plugged in": A Network Analysis of Health-Information Seeking among "Stay-At-Home Moms."

ERIC Educational Resources Information Center

Tardy, Rebecca W.; Hale, Claudia L.

1998-01-01

Examines health-oriented conversations in informal, interpersonal networks. Investigates the network structure, nature of relationships, contents of interactions, and impact of support manifested in a "stay-at-home" mothers' toddlers' play group. Identifies members' roles, and characteristics of opinion leaders, and includes anecdotal…

Influence of Protein Abundance on High-Throughput Protein-Protein Interaction Detection

DTIC Science & Technology

2009-06-05

the interaction data sets we determined, via comparisons with strict randomized simulations , the propensity for essential proteins to selectively...and analysis of high- quality PPI data sets. Materials and Methods We analyzed protein interaction networks for yeast and E. coli determined from Y2H...we reinvestigated the centrality-lethality rule, which implies that proteins having more interactions are more likely to be essential. From analysis

An Approach Based on Social Network Analysis Applied to a Collaborative Learning Experience

ERIC Educational Resources Information Center

Claros, Iván; Cobos, Ruth; Collazos, César A.

2016-01-01

The Social Network Analysis (SNA) techniques allow modelling and analysing the interaction among individuals based on their attributes and relationships. This approach has been used by several researchers in order to measure the social processes in collaborative learning experiences. But oftentimes such measures were calculated at the final state…

Visualization techniques for computer network defense

NASA Astrophysics Data System (ADS)

Beaver, Justin M.; Steed, Chad A.; Patton, Robert M.; Cui, Xiaohui; Schultz, Matthew

2011-06-01

Effective visual analysis of computer network defense (CND) information is challenging due to the volume and complexity of both the raw and analyzed network data. A typical CND is comprised of multiple niche intrusion detection tools, each of which performs network data analysis and produces a unique alerting output. The state-of-the-practice in the situational awareness of CND data is the prevalent use of custom-developed scripts by Information Technology (IT) professionals to retrieve, organize, and understand potential threat events. We propose a new visual analytics framework, called the Oak Ridge Cyber Analytics (ORCA) system, for CND data that allows an operator to interact with all detection tool outputs simultaneously. Aggregated alert events are presented in multiple coordinated views with timeline, cluster, and swarm model analysis displays. These displays are complemented with both supervised and semi-supervised machine learning classifiers. The intent of the visual analytics framework is to improve CND situational awareness, to enable an analyst to quickly navigate and analyze thousands of detected events, and to combine sophisticated data analysis techniques with interactive visualization such that patterns of anomalous activities may be more easily identified and investigated.

Social network analysis of a project-based introductory physics course

NASA Astrophysics Data System (ADS)

Oakley, Christopher

2016-03-01

Research suggests that students benefit from peer interaction and active engagement in the classroom. The quality, nature, effect of these interactions is currently being explored by Physics Education Researchers. Spelman College offers an introductory physics sequence that addresses content and research skills by engaging students in open-ended research projects, a form of Project-Based Learning. Students have been surveyed at regular intervals during the second semester of trigonometry-based course to determine the frequency of interactions in and out of class. These interactions can be with current or past students, tutors, and instructors. This line of inquiry focuses on metrics of Social Network analysis, such as centrality of participants as well as segmentation of groups. Further research will refine and highlight deeper questions regarding student performance in this pedagogy and course sequence.

Predicting community responses to perturbations in the face of imperfect knowledge and network complexity

USGS Publications Warehouse

Novak, Mark; Wootton, J. Timothy; Doak, Daniel F.; Emmerson, Mark; Estes, James A.; Tinker, M. Timothy

2011-01-01

How best to predict the effects of perturbations to ecological communities has been a long-standing goal for both applied and basic ecology. This quest has recently been revived by new empirical data, new analysis methods, and increased computing speed, with the promise that ecologically important insights may be obtainable from a limited knowledge of community interactions. We use empirically based and simulated networks of varying size and connectance to assess two limitations to predicting perturbation responses in multispecies communities: (1) the inaccuracy by which species interaction strengths are empirically quantified and (2) the indeterminacy of species responses due to indirect effects associated with network size and structure. We find that even modest levels of species richness and connectance (∼25 pairwise interactions) impose high requirements for interaction strength estimates because system indeterminacy rapidly overwhelms predictive insights. Nevertheless, even poorly estimated interaction strengths provide greater average predictive certainty than an approach that uses only the sign of each interaction. Our simulations provide guidance in dealing with the trade-offs involved in maximizing the utility of network approaches for predicting dynamics in multispecies communities.

Accurate prediction of protein–protein interactions from sequence alignments using a Bayesian method

PubMed Central

Burger, Lukas; van Nimwegen, Erik

2008-01-01

Accurate and large-scale prediction of protein–protein interactions directly from amino-acid sequences is one of the great challenges in computational biology. Here we present a new Bayesian network method that predicts interaction partners using only multiple alignments of amino-acid sequences of interacting protein domains, without tunable parameters, and without the need for any training examples. We first apply the method to bacterial two-component systems and comprehensively reconstruct two-component signaling networks across all sequenced bacteria. Comparisons of our predictions with known interactions show that our method infers interaction partners genome-wide with high accuracy. To demonstrate the general applicability of our method we show that it also accurately predicts interaction partners in a recent dataset of polyketide synthases. Analysis of the predicted genome-wide two-component signaling networks shows that cognates (interacting kinase/regulator pairs, which lie adjacent on the genome) and orphans (which lie isolated) form two relatively independent components of the signaling network in each genome. In addition, while most genes are predicted to have only a small number of interaction partners, we find that 10% of orphans form a separate class of ‘hub' nodes that distribute and integrate signals to and from up to tens of different interaction partners. PMID:18277381

Comparing species interaction networks along environmental gradients.

PubMed

Pellissier, Loïc; Albouy, Camille; Bascompte, Jordi; Farwig, Nina; Graham, Catherine; Loreau, Michel; Maglianesi, Maria Alejandra; Melián, Carlos J; Pitteloud, Camille; Roslin, Tomas; Rohr, Rudolf; Saavedra, Serguei; Thuiller, Wilfried; Woodward, Guy; Zimmermann, Niklaus E; Gravel, Dominique

2018-05-01

Knowledge of species composition and their interactions, in the form of interaction networks, is required to understand processes shaping their distribution over time and space. As such, comparing ecological networks along environmental gradients represents a promising new research avenue to understand the organization of life. Variation in the position and intensity of links within networks along environmental gradients may be driven by turnover in species composition, by variation in species abundances and by abiotic influences on species interactions. While investigating changes in species composition has a long tradition, so far only a limited number of studies have examined changes in species interactions between networks, often with differing approaches. Here, we review studies investigating variation in network structures along environmental gradients, highlighting how methodological decisions about standardization can influence their conclusions. Due to their complexity, variation among ecological networks is frequently studied using properties that summarize the distribution or topology of interactions such as number of links, connectance, or modularity. These properties can either be compared directly or using a procedure of standardization. While measures of network structure can be directly related to changes along environmental gradients, standardization is frequently used to facilitate interpretation of variation in network properties by controlling for some co-variables, or via null models. Null models allow comparing the deviation of empirical networks from random expectations and are expected to provide a more mechanistic understanding of the factors shaping ecological networks when they are coupled with functional traits. As an illustration, we compare approaches to quantify the role of trait matching in driving the structure of plant-hummingbird mutualistic networks, i.e. a direct comparison, standardized by null models and hypothesis-based metaweb. Overall, our analysis warns against a comparison of studies that rely on distinct forms of standardization, as they are likely to highlight different signals. Fostering a better understanding of the analytical tools available and the signal they detect will help produce deeper insights into how and why ecological networks vary along environmental gradients. © 2017 Cambridge Philosophical Society.

DiffNet: automatic differential functional summarization of dE-MAP networks.

PubMed

Seah, Boon-Siew; Bhowmick, Sourav S; Dewey, C Forbes

2014-10-01

The study of genetic interaction networks that respond to changing conditions is an emerging research problem. Recently, Bandyopadhyay et al. (2010) proposed a technique to construct a differential network (dE-MAPnetwork) from two static gene interaction networks in order to map the interaction differences between them under environment or condition change (e.g., DNA-damaging agent). This differential network is then manually analyzed to conclude that DNA repair is differentially effected by the condition change. Unfortunately, manual construction of differential functional summary from a dE-MAP network that summarizes all pertinent functional responses is time-consuming, laborious and error-prone, impeding large-scale analysis on it. To this end, we propose DiffNet, a novel data-driven algorithm that leverages Gene Ontology (go) annotations to automatically summarize a dE-MAP network to obtain a high-level map of functional responses due to condition change. We tested DiffNet on the dynamic interaction networks following MMS treatment and demonstrated the superiority of our approach in generating differential functional summaries compared to state-of-the-art graph clustering methods. We studied the effects of parameters in DiffNet in controlling the quality of the summary. We also performed a case study that illustrates its utility. Copyright © 2014 Elsevier Inc. All rights reserved.

Structure-Based Network Analysis of Activation Mechanisms in the ErbB Family of Receptor Tyrosine Kinases: The Regulatory Spine Residues Are Global Mediators of Structural Stability and Allosteric Interactions

PubMed Central

James, Kevin A.; Verkhivker, Gennady M.

2014-01-01

The ErbB protein tyrosine kinases are among the most important cell signaling families and mutation-induced modulation of their activity is associated with diverse functions in biological networks and human disease. We have combined molecular dynamics simulations of the ErbB kinases with the protein structure network modeling to characterize the reorganization of the residue interaction networks during conformational equilibrium changes in the normal and oncogenic forms. Structural stability and network analyses have identified local communities integrated around high centrality sites that correspond to the regulatory spine residues. This analysis has provided a quantitative insight to the mechanism of mutation-induced “superacceptor” activity in oncogenic EGFR dimers. We have found that kinase activation may be determined by allosteric interactions between modules of structurally stable residues that synchronize the dynamics in the nucleotide binding site and the αC-helix with the collective motions of the integrating αF-helix and the substrate binding site. The results of this study have pointed to a central role of the conserved His-Arg-Asp (HRD) motif in the catalytic loop and the Asp-Phe-Gly (DFG) motif as key mediators of structural stability and allosteric communications in the ErbB kinases. We have determined that residues that are indispensable for kinase regulation and catalysis often corresponded to the high centrality nodes within the protein structure network and could be distinguished by their unique network signatures. The optimal communication pathways are also controlled by these nodes and may ensure efficient allosteric signaling in the functional kinase state. Structure-based network analysis has quantified subtle effects of ATP binding on conformational dynamics and stability of the EGFR structures. Consistent with the NMR studies, we have found that nucleotide-induced modulation of the residue interaction networks is not limited to the ATP site, and may enhance allosteric cooperativity with the substrate binding region by increasing communication capabilities of mediating residues. PMID:25427151

Evaluating the Network: A Workflow for Tracking Twitter Interactions Using Social Networking Analysis

ERIC Educational Resources Information Center

Goodier, Sarah

2018-01-01

Networking plays an important role in research projects to build a community and audience around a research area. Using social media is popular in project communication as it provides the ability to engage with a group of followers daily. Such online networking tools provide the advantage of providing nearrealtime data, which can be used to…

Academics and Social Networking Sites: Benefits, Problems and Tensions in Professional Engagement with Online Networking

ERIC Educational Resources Information Center

Jordan, Katy; Weller, Martin

2018-01-01

The web has had a profound effect on the ways people interact, with online social networks arguably playing an important role in changing or augmenting how we connect with others. However, uptake of online social networking by the academic community varies, and needs to be understood. This paper presents an independent, novel analysis of a…

The Effect of Social Network Diagrams on a Virtual Network of Practice: A Korean Case

ERIC Educational Resources Information Center

Jo, Il-Hyun

2009-01-01

This study investigates the effect of the presentation of social network diagrams on virtual team members' interaction behavior via e-mail. E-mail transaction data from 22 software developers in a Korean IT company was analyzed and depicted as diagrams by social network analysis (SNA), and presented to the members as an intervention. Results…

Reverse Nearest Neighbor Search on a Protein-Protein Interaction Network to Infer Protein-Disease Associations.

PubMed

Suratanee, Apichat; Plaimas, Kitiporn

2017-01-01

The associations between proteins and diseases are crucial information for investigating pathological mechanisms. However, the number of known and reliable protein-disease associations is quite small. In this study, an analysis framework to infer associations between proteins and diseases was developed based on a large data set of a human protein-protein interaction network integrating an effective network search, namely, the reverse k -nearest neighbor (R k NN) search. The R k NN search was used to identify an impact of a protein on other proteins. Then, associations between proteins and diseases were inferred statistically. The method using the R k NN search yielded a much higher precision than a random selection, standard nearest neighbor search, or when applying the method to a random protein-protein interaction network. All protein-disease pair candidates were verified by a literature search. Supporting evidence for 596 pairs was identified. In addition, cluster analysis of these candidates revealed 10 promising groups of diseases to be further investigated experimentally. This method can be used to identify novel associations to better understand complex relationships between proteins and diseases.

African American Extended Family and Church-Based Social Network Typologies.

PubMed

Nguyen, Ann W; Chatters, Linda M; Taylor, Robert Joseph

2016-12-01

We examined social network typologies among African American adults and their sociodemographic correlates. Network types were derived from indicators of the family and church networks. Latent class analysis was based on a nationally representative sample of African Americans from the National Survey of American Life. Results indicated four distinct network types: ambivalent, optimal, family centered, and strained. These four types were distinguished by (a) degree of social integration, (b) network composition, and (c) level of negative interactions. In a departure from previous work, a network type composed solely of nonkin was not identified, which may reflect racial differences in social network typologies. Further, the analysis indicated that network types varied by sociodemographic characteristics. Social network typologies have several promising practice implications, as they can inform the development of prevention and intervention programs.

Tightly Regulated Expression of Autographa californica Multicapsid Nucleopolyhedrovirus Immediate Early Genes Emerges from Their Interactions and Possible Collective Behaviors

PubMed Central

Taka, Hitomi; Asano, Shin-ichiro; Matsuura, Yoshiharu; Bando, Hisanori

2015-01-01

To infect their hosts, DNA viruses must successfully initiate the expression of viral genes that control subsequent viral gene expression and manipulate the host environment. Viral genes that are immediately expressed upon infection play critical roles in the early infection process. In this study, we investigated the expression and regulation of five canonical regulatory immediate-early (IE) genes of Autographa californica multicapsid nucleopolyhedrovirus: ie0, ie1, ie2, me53, and pe38. A systematic transient gene-expression analysis revealed that these IE genes are generally transactivators, suggesting the existence of a highly interactive regulatory network. A genetic analysis using gene knockout viruses demonstrated that the expression of these IE genes was tolerant to the single deletions of activator IE genes in the early stage of infection. A network graph analysis on the regulatory relationships observed in the transient expression analysis suggested that the robustness of IE gene expression is due to the organization of the IE gene regulatory network and how each IE gene is activated. However, some regulatory relationships detected by the genetic analysis were contradictory to those observed in the transient expression analysis, especially for IE0-mediated regulation. Statistical modeling, combined with genetic analysis using knockout alleles for ie0 and ie1, showed that the repressor function of ie0 was due to the interaction between ie0 and ie1, not ie0 itself. Taken together, these systematic approaches provided insight into the topology and nature of the IE gene regulatory network. PMID:25816136

An Integrative Analysis of Preeclampsia Based on the Construction of an Extended Composite Network Featuring Protein-Protein Physical Interactions and Transcriptional Relationships

PubMed Central

Vaiman, Daniel; Miralles, Francisco

2016-01-01

Preeclampsia (PE) is a pregnancy disorder defined by hypertension and proteinuria. This disease remains a major cause of maternal and fetal morbidity and mortality. Defective placentation is generally described as being at the root of the disease. The characterization of the transcriptome signature of the preeclamptic placenta has allowed to identify differentially expressed genes (DEGs). However, we still lack a detailed knowledge on how these DEGs impact the function of the placenta. The tools of network biology offer a methodology to explore complex diseases at a systems level. In this study we performed a cross-platform meta-analysis of seven publically available gene expression datasets comparing non-pathological and preeclamptic placentas. Using the rank product algorithm we identified a total of 369 DEGs consistently modified in PE. The DEGs were used as seeds to build both an extended physical protein-protein interactions network and a transcription factors regulatory network. Topological and clustering analysis was conducted to analyze the connectivity properties of the networks. Finally both networks were merged into a composite network which presents an integrated view of the regulatory pathways involved in preeclampsia and the crosstalk between them. This network is a useful tool to explore the relationship between the DEGs and enable hypothesis generation for functional experimentation. PMID:27802351

Integrated web visualizations for protein-protein interaction databases.

PubMed

Jeanquartier, Fleur; Jean-Quartier, Claire; Holzinger, Andreas

2015-06-16

Understanding living systems is crucial for curing diseases. To achieve this task we have to understand biological networks based on protein-protein interactions. Bioinformatics has come up with a great amount of databases and tools that support analysts in exploring protein-protein interactions on an integrated level for knowledge discovery. They provide predictions and correlations, indicate possibilities for future experimental research and fill the gaps to complete the picture of biochemical processes. There are numerous and huge databases of protein-protein interactions used to gain insights into answering some of the many questions of systems biology. Many computational resources integrate interaction data with additional information on molecular background. However, the vast number of diverse Bioinformatics resources poses an obstacle to the goal of understanding. We present a survey of databases that enable the visual analysis of protein networks. We selected M=10 out of N=53 resources supporting visualization, and we tested against the following set of criteria: interoperability, data integration, quantity of possible interactions, data visualization quality and data coverage. The study reveals differences in usability, visualization features and quality as well as the quantity of interactions. StringDB is the recommended first choice. CPDB presents a comprehensive dataset and IntAct lets the user change the network layout. A comprehensive comparison table is available via web. The supplementary table can be accessed on http://tinyurl.com/PPI-DB-Comparison-2015. Only some web resources featuring graph visualization can be successfully applied to interactive visual analysis of protein-protein interaction. Study results underline the necessity for further enhancements of visualization integration in biochemical analysis tools. Identified challenges are data comprehensiveness, confidence, interactive feature and visualization maturing.

Dissortativity and duplications in oral cancer

NASA Astrophysics Data System (ADS)

Shinde, Pramod; Yadav, Alok; Rai, Aparna; Jalan, Sarika

2015-08-01

More than 300 000 new cases worldwide are being diagnosed with oral cancer annually. Complexity of oral cancer renders designing drug targets very difficult. We analyse protein-protein interaction network for the normal and oral cancer tissue and detect crucial changes in the structural properties of the networks in terms of the interactions of the hub proteins and the degree-degree correlations. Further analysis of the spectra of both the networks, while exhibiting universal statistical behaviour, manifest distinction in terms of the zero degeneracy, providing insight to the complexity of the underlying system.

A gene network bioinformatics analysis for pemphigoid autoimmune blistering diseases.

PubMed

Barone, Antonio; Toti, Paolo; Giuca, Maria Rita; Derchi, Giacomo; Covani, Ugo

2015-07-01

In this theoretical study, a text mining search and clustering analysis of data related to genes potentially involved in human pemphigoid autoimmune blistering diseases (PAIBD) was performed using web tools to create a gene/protein interaction network. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was employed to identify a final set of PAIBD-involved genes and to calculate the overall significant interactions among genes: for each gene, the weighted number of links, or WNL, was registered and a clustering procedure was performed using the WNL analysis. Genes were ranked in class (leader, B, C, D and so on, up to orphans). An ontological analysis was performed for the set of 'leader' genes. Using the above-mentioned data network, 115 genes represented the final set; leader genes numbered 7 (intercellular adhesion molecule 1 (ICAM-1), interferon gamma (IFNG), interleukin (IL)-2, IL-4, IL-6, IL-8 and tumour necrosis factor (TNF)), class B genes were 13, whereas the orphans were 24. The ontological analysis attested that the molecular action was focused on extracellular space and cell surface, whereas the activation and regulation of the immunity system was widely involved. Despite the limited knowledge of the present pathologic phenomenon, attested by the presence of 24 genes revealing no protein-protein direct or indirect interactions, the network showed significant pathways gathered in several subgroups: cellular components, molecular functions, biological processes and the pathologic phenomenon obtained from the Kyoto Encyclopaedia of Genes and Genomes (KEGG) database. The molecular basis for PAIBD was summarised and expanded, which will perhaps give researchers promising directions for the identification of new therapeutic targets.

Mourning and Grief on Facebook: An Examination of Motivations for Interacting With the Deceased.

PubMed

Willis, Erin; Ferrucci, Patrick

2017-12-01

Facebook not only changed the way we communicate but also the way we mourn and express grief. The social networking site allows users to interact with deceased users' walls after death. This study utilized textual analysis to categorize Facebook posts ( N = 122) on 30 deceased users' walls according to uses and gratifications theory. Most posts were found to be motivated by entertainment, followed by integration and social interaction. Facebook users posted memories, condolences, and interacted with friends and family members in the deceased user's network. Implications and potential future research are discussed.

Mutation-induced protein interaction kinetics changes affect apoptotic network dynamic properties and facilitate oncogenesis

PubMed Central

Zhao, Linjie; Sun, Tanlin; Pei, Jianfeng; Ouyang, Qi

2015-01-01

It has been a consensus in cancer research that cancer is a disease caused primarily by genomic alterations, especially somatic mutations. However, the mechanism of mutation-induced oncogenesis is not fully understood. Here, we used the mitochondrial apoptotic pathway as a case study and performed a systematic analysis of integrating pathway dynamics with protein interaction kinetics to quantitatively investigate the causal molecular mechanism of mutation-induced oncogenesis. A mathematical model of the regulatory network was constructed to establish the functional role of dynamic bifurcation in the apoptotic process. The oncogenic mutation enrichment of each of the protein functional domains involved was found strongly correlated with the parameter sensitivity of the bifurcation point. We further dissected the causal mechanism underlying this correlation by evaluating the mutational influence on protein interaction kinetics using molecular dynamics simulation. We analyzed 29 matched mutant–wild-type and 16 matched SNP—wild-type protein systems. We found that the binding kinetics changes reflected by the changes of free energy changes induced by protein interaction mutations, which induce variations in the sensitive parameters of the bifurcation point, were a major cause of apoptosis pathway dysfunction, and mutations involved in sensitive interaction domains show high oncogenic potential. Our analysis provided a molecular basis for connecting protein mutations, protein interaction kinetics, network dynamics properties, and physiological function of a regulatory network. These insights provide a framework for coupling mutation genotype to tumorigenesis phenotype and help elucidate the logic of cancer initiation. PMID:26170328

Pattern Analysis in Social Networks with Dynamic Connections

NASA Astrophysics Data System (ADS)

Wu, Yu; Zhang, Yu

In this paper, we explore how decentralized local interactions of autonomous agents in a network relate to collective behaviors. Most existing work in this area models social network in which agent relations are fixed; instead, we focus on dynamic social networks where agents can rationally adjust their neighborhoods based on their individual interests. We propose a new connection evaluation rule called the Highest Weighted Reward (HWR) rule, with which agents dynamically choose their neighbors in order to maximize their own utilities based on the rewards from previous interactions. Our experiments show that in the 2-action pure coordination game, our system will stabilize to a clustering state where all relationships in the network are rewarded with the optimal payoff. Our experiments also reveal additional interesting patterns in the network.

The Biomolecular Interaction Network Database and related tools 2005 update

PubMed Central

Alfarano, C.; Andrade, C. E.; Anthony, K.; Bahroos, N.; Bajec, M.; Bantoft, K.; Betel, D.; Bobechko, B.; Boutilier, K.; Burgess, E.; Buzadzija, K.; Cavero, R.; D'Abreo, C.; Donaldson, I.; Dorairajoo, D.; Dumontier, M. J.; Dumontier, M. R.; Earles, V.; Farrall, R.; Feldman, H.; Garderman, E.; Gong, Y.; Gonzaga, R.; Grytsan, V.; Gryz, E.; Gu, V.; Haldorsen, E.; Halupa, A.; Haw, R.; Hrvojic, A.; Hurrell, L.; Isserlin, R.; Jack, F.; Juma, F.; Khan, A.; Kon, T.; Konopinsky, S.; Le, V.; Lee, E.; Ling, S.; Magidin, M.; Moniakis, J.; Montojo, J.; Moore, S.; Muskat, B.; Ng, I.; Paraiso, J. P.; Parker, B.; Pintilie, G.; Pirone, R.; Salama, J. J.; Sgro, S.; Shan, T.; Shu, Y.; Siew, J.; Skinner, D.; Snyder, K.; Stasiuk, R.; Strumpf, D.; Tuekam, B.; Tao, S.; Wang, Z.; White, M.; Willis, R.; Wolting, C.; Wong, S.; Wrong, A.; Xin, C.; Yao, R.; Yates, B.; Zhang, S.; Zheng, K.; Pawson, T.; Ouellette, B. F. F.; Hogue, C. W. V.

2005-01-01

The Biomolecular Interaction Network Database (BIND) (http://bind.ca) archives biomolecular interaction, reaction, complex and pathway information. Our aim is to curate the details about molecular interactions that arise from published experimental research and to provide this information, as well as tools to enable data analysis, freely to researchers worldwide. BIND data are curated into a comprehensive machine-readable archive of computable information and provides users with methods to discover interactions and molecular mechanisms. BIND has worked to develop new methods for visualization that amplify the underlying annotation of genes and proteins to facilitate the study of molecular interaction networks. BIND has maintained an open database policy since its inception in 1999. Data growth has proceeded at a tremendous rate, approaching over 100 000 records. New services provided include a new BIND Query and Submission interface, a Standard Object Access Protocol service and the Small Molecule Interaction Database (http://smid.blueprint.org) that allows users to determine probable small molecule binding sites of new sequences and examine conserved binding residues. PMID:15608229

A network model of genomic hormone interactions underlying dementia and its translational validation through serendipitous off-target effect

PubMed Central

2013-01-01

Background While the majority of studies have focused on the association between sex hormones and dementia, emerging evidence supports the role of other hormone signals in increasing dementia risk. However, due to the lack of an integrated view on mechanistic interactions of hormone signaling pathways associated with dementia, molecular mechanisms through which hormones contribute to the increased risk of dementia has remained unclear and capacity of translating hormone signals to potential therapeutic and diagnostic applications in relation to dementia has been undervalued. Methods Using an integrative knowledge- and data-driven approach, a global hormone interaction network in the context of dementia was constructed, which was further filtered down to a model of convergent hormone signaling pathways. This model was evaluated for its biological and clinical relevance through pathway recovery test, evidence-based analysis, and biomarker-guided analysis. Translational validation of the model was performed using the proposed novel mechanism discovery approach based on ‘serendipitous off-target effects’. Results Our results reveal the existence of a well-connected hormone interaction network underlying dementia. Seven hormone signaling pathways converge at the core of the hormone interaction network, which are shown to be mechanistically linked to the risk of dementia. Amongst these pathways, estrogen signaling pathway takes the major part in the model and insulin signaling pathway is analyzed for its association to learning and memory functions. Validation of the model through serendipitous off-target effects suggests that hormone signaling pathways substantially contribute to the pathogenesis of dementia. Conclusions The integrated network model of hormone interactions underlying dementia may serve as an initial translational platform for identifying potential therapeutic targets and candidate biomarkers for dementia-spectrum disorders such as Alzheimer’s disease. PMID:23885764

AlignNemo: a local network alignment method to integrate homology and topology.

PubMed

Ciriello, Giovanni; Mina, Marco; Guzzi, Pietro H; Cannataro, Mario; Guerra, Concettina

2012-01-01

Local network alignment is an important component of the analysis of protein-protein interaction networks that may lead to the identification of evolutionary related complexes. We present AlignNemo, a new algorithm that, given the networks of two organisms, uncovers subnetworks of proteins that relate in biological function and topology of interactions. The discovered conserved subnetworks have a general topology and need not to correspond to specific interaction patterns, so that they more closely fit the models of functional complexes proposed in the literature. The algorithm is able to handle sparse interaction data with an expansion process that at each step explores the local topology of the networks beyond the proteins directly interacting with the current solution. To assess the performance of AlignNemo, we ran a series of benchmarks using statistical measures as well as biological knowledge. Based on reference datasets of protein complexes, AlignNemo shows better performance than other methods in terms of both precision and recall. We show our solutions to be biologically sound using the concept of semantic similarity applied to Gene Ontology vocabularies. The binaries of AlignNemo and supplementary details about the algorithms and the experiments are available at: sourceforge.net/p/alignnemo.

Detecting recurrent gene mutation in interaction network context using multi-scale graph diffusion.

PubMed

Babaei, Sepideh; Hulsman, Marc; Reinders, Marcel; de Ridder, Jeroen

2013-01-23

Delineating the molecular drivers of cancer, i.e. determining cancer genes and the pathways which they deregulate, is an important challenge in cancer research. In this study, we aim to identify pathways of frequently mutated genes by exploiting their network neighborhood encoded in the protein-protein interaction network. To this end, we introduce a multi-scale diffusion kernel and apply it to a large collection of murine retroviral insertional mutagenesis data. The diffusion strength plays the role of scale parameter, determining the size of the network neighborhood that is taken into account. As a result, in addition to detecting genes with frequent mutations in their genomic vicinity, we find genes that harbor frequent mutations in their interaction network context. We identify densely connected components of known and putatively novel cancer genes and demonstrate that they are strongly enriched for cancer related pathways across the diffusion scales. Moreover, the mutations in the clusters exhibit a significant pattern of mutual exclusion, supporting the conjecture that such genes are functionally linked. Using multi-scale diffusion kernel, various infrequently mutated genes are found to harbor significant numbers of mutations in their interaction network neighborhood. Many of them are well-known cancer genes. The results demonstrate the importance of defining recurrent mutations while taking into account the interaction network context. Importantly, the putative cancer genes and networks detected in this study are found to be significant at different diffusion scales, confirming the necessity of a multi-scale analysis.

Neuroimaging Study of Alpha and Beta EEG Biofeedback Effects on Neural Networks.

PubMed

Shtark, Mark B; Kozlova, Lyudmila I; Bezmaternykh, Dmitriy D; Mel'nikov, Mikhail Ye; Savelov, Andrey A; Sokhadze, Estate M

2018-06-01

Neural networks interaction was studied in healthy men (20-35 years old) who underwent 20 sessions of EEG biofeedback training outside the MRI scanner, with concurrent fMRI-EEG scans at the beginning, middle, and end of the course. The study recruited 35 subjects for EEG biofeedback, but only 18 of them were considered as "successful" in self-regulation of target EEG bands during the whole course of training. Results of fMRI analysis during EEG biofeedback are reported only for these "successful" trainees. The experimental group (N = 23 total, N = 13 "successful") upregulated the power of alpha rhythm, while the control group (N = 12 total, N = 5 "successful") beta rhythm, with the protocol instructions being as for alpha training in both. The acquisition of the stable skills of alpha self-regulation was followed by the weakening of the irrelevant links between the cerebellum and visuospatial network (VSN), as well as between the VSN, the right executive control network (RECN), and the cuneus. It was also found formation of a stable complex based on the interaction of the precuneus, the cuneus, the VSN, and the high level visuospatial network (HVN), along with the strengthening of the interaction of the anterior salience network (ASN) with the precuneus. In the control group, beta enhancement training was accompanied by weakening of interaction between the precuneus and the default mode network, and a decrease in connectivity between the cuneus and the primary visual network (PVN). The differences between the alpha training group and the control group increased successively during training. Alpha training was characterized by a less pronounced interaction of the network formed by the PVN and the HVN, as well as by an increased interaction of the cerebellum with the precuneus and the RECN. The study demonstrated the differences in the structure and interaction of neural networks involved into alpha and beta generating systems forming and functioning, which should be taken into account during planning neurofeedback interventions. Possibility of using fMRI-guided biofeedback organized according to the described neural networks interaction may advance more accurate targeting specific symptoms during neurotherapy.

Detection of Significant Pneumococcal Meningitis Biomarkers by Ego Network.

PubMed

Wang, Qian; Lou, Zhifeng; Zhai, Liansuo; Zhao, Haibin

2017-06-01

To identify significant biomarkers for detection of pneumococcal meningitis based on ego network. Based on the gene expression data of pneumococcal meningitis and global protein-protein interactions (PPIs) data recruited from open access databases, the authors constructed a differential co-expression network (DCN) to identify pneumococcal meningitis biomarkers in a network view. Here EgoNet algorithm was employed to screen the significant ego networks that could accurately distinguish pneumococcal meningitis from healthy controls, by sequentially seeking ego genes, searching candidate ego networks, refinement of candidate ego networks and significance analysis to identify ego networks. Finally, the functional inference of the ego networks was performed to identify significant pathways for pneumococcal meningitis. By differential co-expression analysis, the authors constructed the DCN that covered 1809 genes and 3689 interactions. From the DCN, a total of 90 ego genes were identified. Starting from these ego genes, three significant ego networks (Module 19, Module 70 and Module 71) that could predict clinical outcomes for pneumococcal meningitis were identified by EgoNet algorithm, and the corresponding ego genes were GMNN, MAD2L1 and TPX2, respectively. Pathway analysis showed that these three ego networks were related to CDT1 association with the CDC6:ORC:origin complex, inactivation of APC/C via direct inhibition of the APC/C complex pathway, and DNA strand elongation, respectively. The authors successfully screened three significant ego modules which could accurately predict the clinical outcomes for pneumococcal meningitis and might play important roles in host response to pathogen infection in pneumococcal meningitis.

Multi-focus and multi-level techniques for visualization and analysis of networks with thematic data

NASA Astrophysics Data System (ADS)

Cossalter, Michele; Mengshoel, Ole J.; Selker, Ted

2013-01-01

Information-rich data sets bring several challenges in the areas of visualization and analysis, even when associated with node-link network visualizations. This paper presents an integration of multi-focus and multi-level techniques that enable interactive, multi-step comparisons in node-link networks. We describe NetEx, a visualization tool that enables users to simultaneously explore different parts of a network and its thematic data, such as time series or conditional probability tables. NetEx, implemented as a Cytoscape plug-in, has been applied to the analysis of electrical power networks, Bayesian networks, and the Enron e-mail repository. In this paper we briefly discuss visualization and analysis of the Enron social network, but focus on data from an electrical power network. Specifically, we demonstrate how NetEx supports the analytical task of electrical power system fault diagnosis. Results from a user study with 25 subjects suggest that NetEx enables more accurate isolation of complex faults compared to an especially designed software tool.

Experiments and Analysis on a Computer Interface to an Information-Retrieval Network.

ERIC Educational Resources Information Center

Marcus, Richard S.; Reintjes, J. Francis

A primary goal of this project was to develop an interface that would provide direct access for inexperienced users to existing online bibliographic information retrieval networks. The experiment tested the concept of a virtual-system mode of access to a network of heterogeneous interactive retrieval systems and databases. An experimental…

Analysis of a summary network of co-infection in humans reveals that parasites interact most via shared resources

PubMed Central

Griffiths, Emily C.; Pedersen, Amy B.; Fenton, Andy; Petchey, Owen L.

2014-01-01

Simultaneous infection by multiple parasite species (viruses, bacteria, helminths, protozoa or fungi) is commonplace. Most reports show co-infected humans to have worse health than those with single infections. However, we have little understanding of how co-infecting parasites interact within human hosts. We used data from over 300 published studies to construct a network that offers the first broad indications of how groups of co-infecting parasites tend to interact. The network had three levels comprising parasites, the resources they consume and the immune responses they elicit, connected by potential, observed and experimentally proved links. Pairs of parasite species had most potential to interact indirectly through shared resources, rather than through immune responses or other parasites. In addition, the network comprised 10 tightly knit groups, eight of which were associated with particular body parts, and seven of which were dominated by parasite–resource links. Reported co-infection in humans is therefore structured by physical location within the body, with bottom-up, resource-mediated processes most often influencing how, where and which co-infecting parasites interact. The many indirect interactions show how treating an infection could affect other infections in co-infected patients, but the compartmentalized structure of the network will limit how far these indirect effects are likely to spread. PMID:24619434

Analysis of a summary network of co-infection in humans reveals that parasites interact most via shared resources.

PubMed

Griffiths, Emily C; Pedersen, Amy B; Fenton, Andy; Petchey, Owen L

2014-05-07

Simultaneous infection by multiple parasite species (viruses, bacteria, helminths, protozoa or fungi) is commonplace. Most reports show co-infected humans to have worse health than those with single infections. However, we have little understanding of how co-infecting parasites interact within human hosts. We used data from over 300 published studies to construct a network that offers the first broad indications of how groups of co-infecting parasites tend to interact. The network had three levels comprising parasites, the resources they consume and the immune responses they elicit, connected by potential, observed and experimentally proved links. Pairs of parasite species had most potential to interact indirectly through shared resources, rather than through immune responses or other parasites. In addition, the network comprised 10 tightly knit groups, eight of which were associated with particular body parts, and seven of which were dominated by parasite-resource links. Reported co-infection in humans is therefore structured by physical location within the body, with bottom-up, resource-mediated processes most often influencing how, where and which co-infecting parasites interact. The many indirect interactions show how treating an infection could affect other infections in co-infected patients, but the compartmentalized structure of the network will limit how far these indirect effects are likely to spread.

Breakdown of interdependent directed networks.

PubMed

Liu, Xueming; Stanley, H Eugene; Gao, Jianxi

2016-02-02

Increasing evidence shows that real-world systems interact with one another via dependency connectivities. Failing connectivities are the mechanism behind the breakdown of interacting complex systems, e.g., blackouts caused by the interdependence of power grids and communication networks. Previous research analyzing the robustness of interdependent networks has been limited to undirected networks. However, most real-world networks are directed, their in-degrees and out-degrees may be correlated, and they are often coupled to one another as interdependent directed networks. To understand the breakdown and robustness of interdependent directed networks, we develop a theoretical framework based on generating functions and percolation theory. We find that for interdependent Erdős-Rényi networks the directionality within each network increases their vulnerability and exhibits hybrid phase transitions. We also find that the percolation behavior of interdependent directed scale-free networks with and without degree correlations is so complex that two criteria are needed to quantify and compare their robustness: the percolation threshold and the integrated size of the giant component during an entire attack process. Interestingly, we find that the in-degree and out-degree correlations in each network layer increase the robustness of interdependent degree heterogeneous networks that most real networks are, but decrease the robustness of interdependent networks with homogeneous degree distribution and with strong coupling strengths. Moreover, by applying our theoretical analysis to real interdependent international trade networks, we find that the robustness of these real-world systems increases with the in-degree and out-degree correlations, confirming our theoretical analysis.

Network diffusion-based analysis of high-throughput data for the detection of differentially enriched modules

PubMed Central

Bersanelli, Matteo; Mosca, Ettore; Remondini, Daniel; Castellani, Gastone; Milanesi, Luciano

2016-01-01

A relation exists between network proximity of molecular entities in interaction networks, functional similarity and association with diseases. The identification of network regions associated with biological functions and pathologies is a major goal in systems biology. We describe a network diffusion-based pipeline for the interpretation of different types of omics in the context of molecular interaction networks. We introduce the network smoothing index, a network-based quantity that allows to jointly quantify the amount of omics information in genes and in their network neighbourhood, using network diffusion to define network proximity. The approach is applicable to both descriptive and inferential statistics calculated on omics data. We also show that network resampling, applied to gene lists ranked by quantities derived from the network smoothing index, indicates the presence of significantly connected genes. As a proof of principle, we identified gene modules enriched in somatic mutations and transcriptional variations observed in samples of prostate adenocarcinoma (PRAD). In line with the local hypothesis, network smoothing index and network resampling underlined the existence of a connected component of genes harbouring molecular alterations in PRAD. PMID:27731320

Interactive Planning under Uncertainty with Casual Modeling and Analysis

DTIC Science & Technology

2006-01-01

Tool ( CAT ), a system for creating and analyzing causal models similar to Bayes networks. In order to use CAT as a tool for planning, users go through...an iterative process in which they use CAT to create and an- alyze alternative plans. One of the biggest difficulties is that the number of possible...Causal Analysis Tool ( CAT ), which is a tool for representing and analyzing causal networks sim- ilar to Bayesian networks. In order to represent plans

Genomic analysis of regulatory network dynamics reveals large topological changes

NASA Astrophysics Data System (ADS)

Luscombe, Nicholas M.; Madan Babu, M.; Yu, Haiyuan; Snyder, Michael; Teichmann, Sarah A.; Gerstein, Mark

2004-09-01

Network analysis has been applied widely, providing a unifying language to describe disparate systems ranging from social interactions to power grids. It has recently been used in molecular biology, but so far the resulting networks have only been analysed statically. Here we present the dynamics of a biological network on a genomic scale, by integrating transcriptional regulatory information and gene-expression data for multiple conditions in Saccharomyces cerevisiae. We develop an approach for the statistical analysis of network dynamics, called SANDY, combining well-known global topological measures, local motifs and newly derived statistics. We uncover large changes in underlying network architecture that are unexpected given current viewpoints and random simulations. In response to diverse stimuli, transcription factors alter their interactions to varying degrees, thereby rewiring the network. A few transcription factors serve as permanent hubs, but most act transiently only during certain conditions. By studying sub-network structures, we show that environmental responses facilitate fast signal propagation (for example, with short regulatory cascades), whereas the cell cycle and sporulation direct temporal progression through multiple stages (for example, with highly inter-connected transcription factors). Indeed, to drive the latter processes forward, phase-specific transcription factors inter-regulate serially, and ubiquitously active transcription factors layer above them in a two-tiered hierarchy. We anticipate that many of the concepts presented here-particularly the large-scale topological changes and hub transience-will apply to other biological networks, including complex sub-systems in higher eukaryotes.

Semantic web for integrated network analysis in biomedicine.

PubMed

Chen, Huajun; Ding, Li; Wu, Zhaohui; Yu, Tong; Dhanapalan, Lavanya; Chen, Jake Y

2009-03-01

The Semantic Web technology enables integration of heterogeneous data on the World Wide Web by making the semantics of data explicit through formal ontologies. In this article, we survey the feasibility and state of the art of utilizing the Semantic Web technology to represent, integrate and analyze the knowledge in various biomedical networks. We introduce a new conceptual framework, semantic graph mining, to enable researchers to integrate graph mining with ontology reasoning in network data analysis. Through four case studies, we demonstrate how semantic graph mining can be applied to the analysis of disease-causal genes, Gene Ontology category cross-talks, drug efficacy analysis and herb-drug interactions analysis.

The College Football Student-Athlete's Academic Experience: Network Analysis and Model Development

ERIC Educational Resources Information Center

Young, Kyle McLendon

2010-01-01

A grounded theory research study employing network analysis as a means of facilitating the latter stages of the coding process was conducted at a selective university that competes at the highest level of college football. The purpose of the study was to develop a better understanding of how interactive dynamics and controlling mechanisms, such as…

Parallel versus Serial Processing Dependencies in the Perisylvian Speech Network: A Granger Analysis of Intracranial EEG Data

ERIC Educational Resources Information Center

Gow, David W., Jr.; Keller, Corey J.; Eskandar, Emad; Meng, Nate; Cash, Sydney S.

2009-01-01

In this work, we apply Granger causality analysis to high spatiotemporal resolution intracranial EEG (iEEG) data to examine how different components of the left perisylvian language network interact during spoken language perception. The specific focus is on the characterization of serial versus parallel processing dependencies in the dominant…

Working at Community Boundaries: A Micro-Analysis of the Activist's Role in Participatory Learning Networks

ERIC Educational Resources Information Center

Thorpe, Mary; Kubiak, Chris

2005-01-01

The interaction of agency and context in workplace learning is explored through a micro-analysis of the implementation of networked learning communities in schools in England. Interviews with local activists show evidence of co-participation between individuals' responses and their workplace roles and experience as they take up the opportunity to…

Protein Interaction Networks Reveal Novel Autism Risk Genes within GWAS Statistical Noise

PubMed Central

Correia, Catarina; Oliveira, Guiomar; Vicente, Astrid M.

2014-01-01

Genome-wide association studies (GWAS) for Autism Spectrum Disorder (ASD) thus far met limited success in the identification of common risk variants, consistent with the notion that variants with small individual effects cannot be detected individually in single SNP analysis. To further capture disease risk gene information from ASD association studies, we applied a network-based strategy to the Autism Genome Project (AGP) and the Autism Genetics Resource Exchange GWAS datasets, combining family-based association data with Human Protein-Protein interaction (PPI) data. Our analysis showed that autism-associated proteins at higher than conventional levels of significance (P<0.1) directly interact more than random expectation and are involved in a limited number of interconnected biological processes, indicating that they are functionally related. The functionally coherent networks generated by this approach contain ASD-relevant disease biology, as demonstrated by an improved positive predictive value and sensitivity in retrieving known ASD candidate genes relative to the top associated genes from either GWAS, as well as a higher gene overlap between the two ASD datasets. Analysis of the intersection between the networks obtained from the two ASD GWAS and six unrelated disease datasets identified fourteen genes exclusively present in the ASD networks. These are mostly novel genes involved in abnormal nervous system phenotypes in animal models, and in fundamental biological processes previously implicated in ASD, such as axon guidance, cell adhesion or cytoskeleton organization. Overall, our results highlighted novel susceptibility genes previously hidden within GWAS statistical “noise” that warrant further analysis for causal variants. PMID:25409314

Protein interaction networks reveal novel autism risk genes within GWAS statistical noise.

PubMed

Correia, Catarina; Oliveira, Guiomar; Vicente, Astrid M

2014-01-01

Genome-wide association studies (GWAS) for Autism Spectrum Disorder (ASD) thus far met limited success in the identification of common risk variants, consistent with the notion that variants with small individual effects cannot be detected individually in single SNP analysis. To further capture disease risk gene information from ASD association studies, we applied a network-based strategy to the Autism Genome Project (AGP) and the Autism Genetics Resource Exchange GWAS datasets, combining family-based association data with Human Protein-Protein interaction (PPI) data. Our analysis showed that autism-associated proteins at higher than conventional levels of significance (P<0.1) directly interact more than random expectation and are involved in a limited number of interconnected biological processes, indicating that they are functionally related. The functionally coherent networks generated by this approach contain ASD-relevant disease biology, as demonstrated by an improved positive predictive value and sensitivity in retrieving known ASD candidate genes relative to the top associated genes from either GWAS, as well as a higher gene overlap between the two ASD datasets. Analysis of the intersection between the networks obtained from the two ASD GWAS and six unrelated disease datasets identified fourteen genes exclusively present in the ASD networks. These are mostly novel genes involved in abnormal nervous system phenotypes in animal models, and in fundamental biological processes previously implicated in ASD, such as axon guidance, cell adhesion or cytoskeleton organization. Overall, our results highlighted novel susceptibility genes previously hidden within GWAS statistical "noise" that warrant further analysis for causal variants.

Crucial role of strategy updating for coexistence of strategies in interaction networks.

PubMed

Zhang, Jianlei; Zhang, Chunyan; Cao, Ming; Weissing, Franz J

2015-04-01

Network models are useful tools for studying the dynamics of social interactions in a structured population. After a round of interactions with the players in their local neighborhood, players update their strategy based on the comparison of their own payoff with the payoff of one of their neighbors. Here we show that the assumptions made on strategy updating are of crucial importance for the strategy dynamics. In the first step, we demonstrate that seemingly small deviations from the standard assumptions on updating have major implications for the evolutionary outcome of two cooperation games: cooperation can more easily persist in a Prisoner's Dilemma game, while it can go more easily extinct in a Snowdrift game. To explain these outcomes, we develop a general model for the updating of states in a network that allows us to derive conditions for the steady-state coexistence of states (or strategies). The analysis reveals that coexistence crucially depends on the number of agents consulted for updating. We conclude that updating rules are as important for evolution on a network as network structure and the nature of the interaction.

Crucial role of strategy updating for coexistence of strategies in interaction networks

NASA Astrophysics Data System (ADS)

Zhang, Jianlei; Zhang, Chunyan; Cao, Ming; Weissing, Franz J.

2015-04-01

Network models are useful tools for studying the dynamics of social interactions in a structured population. After a round of interactions with the players in their local neighborhood, players update their strategy based on the comparison of their own payoff with the payoff of one of their neighbors. Here we show that the assumptions made on strategy updating are of crucial importance for the strategy dynamics. In the first step, we demonstrate that seemingly small deviations from the standard assumptions on updating have major implications for the evolutionary outcome of two cooperation games: cooperation can more easily persist in a Prisoner's Dilemma game, while it can go more easily extinct in a Snowdrift game. To explain these outcomes, we develop a general model for the updating of states in a network that allows us to derive conditions for the steady-state coexistence of states (or strategies). The analysis reveals that coexistence crucially depends on the number of agents consulted for updating. We conclude that updating rules are as important for evolution on a network as network structure and the nature of the interaction.

High-order interactions observed in multi-task intrinsic networks are dominant indicators of aberrant brain function in schizophrenia

PubMed Central

Plis, Sergey M; Sui, Jing; Lane, Terran; Roy, Sushmita; Clark, Vincent P; Potluru, Vamsi K; Huster, Rene J; Michael, Andrew; Sponheim, Scott R; Weisend, Michael P; Calhoun, Vince D

2013-01-01

Identifying the complex activity relationships present in rich, modern neuroimaging data sets remains a key challenge for neuroscience. The problem is hard because (a) the underlying spatial and temporal networks may be nonlinear and multivariate and (b) the observed data may be driven by numerous latent factors. Further, modern experiments often produce data sets containing multiple stimulus contexts or tasks processed by the same subjects. Fusing such multi-session data sets may reveal additional structure, but raises further statistical challenges. We present a novel analysis method for extracting complex activity networks from such multifaceted imaging data sets. Compared to previous methods, we choose a new point in the trade-off space, sacrificing detailed generative probability models and explicit latent variable inference in order to achieve robust estimation of multivariate, nonlinear group factors (“network clusters”). We apply our method to identify relationships of task-specific intrinsic networks in schizophrenia patients and control subjects from a large fMRI study. After identifying network-clusters characterized by within- and between-task interactions, we find significant differences between patient and control groups in interaction strength among networks. Our results are consistent with known findings of brain regions exhibiting deviations in schizophrenic patients. However, we also find high-order, nonlinear interactions that discriminate groups but that are not detected by linear, pair-wise methods. We additionally identify high-order relationships that provide new insights into schizophrenia but that have not been found by traditional univariate or second-order methods. Overall, our approach can identify key relationships that are missed by existing analysis methods, without losing the ability to find relationships that are known to be important. PMID:23876245

An interactional network of genes involved in chitin synthesis in Saccharomyces cerevisiae

PubMed Central

Lesage, Guillaume; Shapiro, Jesse; Specht, Charles A; Sdicu, Anne-Marie; Ménard, Patrice; Hussein, Shamiza; Tong, Amy Hin Yan; Boone, Charles; Bussey, Howard

2005-01-01

Background In S. cerevisiae the β-1,4-linked N-acetylglucosamine polymer, chitin, is synthesized by a family of 3 specialized but interacting chitin synthases encoded by CHS1, CHS2 and CHS3. Chs2p makes chitin in the primary septum, while Chs3p makes chitin in the lateral cell wall and in the bud neck, and can partially compensate for the lack of Chs2p. Chs3p requires a pathway of Bni4p, Chs4p, Chs5p, Chs6p and Chs7p for its localization and activity. Chs1p is thought to have a septum repair function after cell separation. To further explore interactions in the chitin synthase family and to find processes buffering chitin synthesis, we compiled a genetic interaction network of genes showing synthetic interactions with CHS1, CHS3 and genes involved in Chs3p localization and function and made a phenotypic analysis of their mutants. Results Using deletion mutants in CHS1, CHS3, CHS4, CHS5, CHS6, CHS7 and BNI4 in a synthetic genetic array analysis we assembled a network of 316 interactions among 163 genes. The interaction network with CHS3, CHS4, CHS5, CHS6, CHS7 or BNI4 forms a dense neighborhood, with many genes functioning in cell wall assembly or polarized secretion. Chitin levels were altered in 54 of the mutants in individually deleted genes, indicating a functional relationship between them and chitin synthesis. 32 of these mutants triggered the chitin stress response, with elevated chitin levels and a dependence on CHS3. A large fraction of the CHS1-interaction set was distinct from that of the CHS3 network, indicating broad roles for Chs1p in buffering both Chs2p function and more global cell wall robustness. Conclusion Based on their interaction patterns and chitin levels we group interacting mutants into functional categories. Genes interacting with CHS3 are involved in the amelioration of cell wall defects and in septum or bud neck chitin synthesis, and we newly assign a number of genes to these functions. Our genetic analysis of genes not interacting with CHS3 indicate expanded roles for Chs4p, Chs5p and Chs6p in secretory protein trafficking and of Bni4p in bud neck organization. PMID:15715908

Exploring the interactions of the RAS family in the human protein network and their potential implications in RAS-directed therapies

PubMed Central

Bueno, Anibal; Morilla, Ian; Diez, Diego; Moya-Garcia, Aurelio A.; Lozano, José; Ranea, Juan A.G.

2016-01-01

RAS proteins are the founding members of the RAS superfamily of GTPases. They are involved in key signaling pathways regulating essential cellular functions such as cell growth and differentiation. As a result, their deregulation by inactivating mutations often results in aberrant cell proliferation and cancer. With the exception of the relatively well-known KRAS, HRAS and NRAS proteins, little is known about how the interactions of the other RAS human paralogs affect cancer evolution and response to treatment. In this study we performed a comprehensive analysis of the relationship between the phylogeny of RAS proteins and their location in the protein interaction network. This analysis was integrated with the structural analysis of conserved positions in available 3D structures of RAS complexes. Our results show that many RAS proteins with divergent sequences are found close together in the human interactome. We found specific conserved amino acid positions in this group that map to the binding sites of RAS with many of their signaling effectors, suggesting that these pairs could share interacting partners. These results underscore the potential relevance of cross-talking in the RAS signaling network, which should be taken into account when considering the inhibitory activity of drugs targeting specific RAS oncoproteins. This study broadens our understanding of the human RAS signaling network and stresses the importance of considering its potential cross-talk in future therapies. PMID:27713118

Competing endogenous RNA regulatory network in papillary thyroid carcinoma.

PubMed

Chen, Shouhua; Fan, Xiaobin; Gu, He; Zhang, Lili; Zhao, Wenhua

2018-05-11

The present study aimed to screen all types of RNAs involved in the development of papillary thyroid carcinoma (PTC). RNA‑sequencing data of PTC and normal samples were used for screening differentially expressed (DE) microRNAs (DE‑miRNAs), long non‑coding RNAs (DE‑lncRNAs) and genes (DEGs). Subsequently, lncRNA‑miRNA, miRNA‑gene (that is, miRNA‑mRNA) and gene‑gene interaction pairs were extracted and used to construct regulatory networks. Feature genes in the miRNA‑mRNA network were identified by topological analysis and recursive feature elimination analysis. A support vector machine (SVM) classifier was built using 15 feature genes, and its classification effect was validated using two microarray data sets that were downloaded from the Gene Expression Omnibus (GEO) database. In addition, Gene Ontology function and Kyoto Encyclopedia Genes and Genomes pathway enrichment analyses were conducted for genes identified in the ceRNA network. A total of 506 samples, including 447 tumor samples and 59 normal samples, were obtained from The Cancer Genome Atlas (TCGA); 16 DE‑lncRNAs, 917 DEGs and 30 DE‑miRNAs were screened. The miRNA‑mRNA regulatory network comprised 353 nodes and 577 interactions. From these data, 15 feature genes with high predictive precision (>95%) were extracted from the network and were used to form an SVM classifier with an accuracy of 96.05% (486/506) for PTC samples downloaded from TCGA, and accuracies of 96.81 and 98.46% for GEO downloaded data sets. The ceRNA regulatory network comprised 596 lines (or interactions) and 365 nodes. Genes in the ceRNA network were significantly enriched in 'neuron development', 'differentiation', 'neuroactive ligand‑receptor interaction', 'metabolism of xenobiotics by cytochrome P450', 'drug metabolism' and 'cytokine‑cytokine receptor interaction' pathways. Hox transcript antisense RNA, miRNA‑206 and kallikrein‑related peptidase 10 were nodes in the ceRNA regulatory network of the selected feature gene, and they may serve import roles in the development of PTC.

Brain-inspired cheminformatics of drug-target brain interactome, synthesis, and assay of TVP1022 derivatives.

PubMed

Romero-Durán, Francisco J; Alonso, Nerea; Yañez, Matilde; Caamaño, Olga; García-Mera, Xerardo; González-Díaz, Humberto

2016-04-01

The use of Cheminformatics tools is gaining importance in the field of translational research from Medicinal Chemistry to Neuropharmacology. In particular, we need it for the analysis of chemical information on large datasets of bioactive compounds. These compounds form large multi-target complex networks (drug-target interactome network) resulting in a very challenging data analysis problem. Artificial Neural Network (ANN) algorithms may help us predict the interactions of drugs and targets in CNS interactome. In this work, we trained different ANN models able to predict a large number of drug-target interactions. These models predict a dataset of thousands of interactions of central nervous system (CNS) drugs characterized by > 30 different experimental measures in >400 different experimental protocols for >150 molecular and cellular targets present in 11 different organisms (including human). The model was able to classify cases of non-interacting vs. interacting drug-target pairs with satisfactory performance. A second aim focus on two main directions: the synthesis and assay of new derivatives of TVP1022 (S-analogues of rasagiline) and the comparison with other rasagiline derivatives recently reported. Finally, we used the best of our models to predict drug-target interactions for the best new synthesized compound against a large number of CNS protein targets. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dynamics of Disagreement: Large-Scale Temporal Network Analysis Reveals Negative Interactions in Online Collaboration

NASA Astrophysics Data System (ADS)

Tsvetkova, Milena; García-Gavilanes, Ruth; Yasseri, Taha

2016-11-01

Disagreement and conflict are a fact of social life. However, negative interactions are rarely explicitly declared and recorded and this makes them hard for scientists to study. In an attempt to understand the structural and temporal features of negative interactions in the community, we use complex network methods to analyze patterns in the timing and configuration of reverts of article edits to Wikipedia. We investigate how often and how fast pairs of reverts occur compared to a null model in order to control for patterns that are natural to the content production or are due to the internal rules of Wikipedia. Our results suggest that Wikipedia editors systematically revert the same person, revert back their reverter, and come to defend a reverted editor. We further relate these interactions to the status of the involved editors. Even though the individual reverts might not necessarily be negative social interactions, our analysis points to the existence of certain patterns of negative social dynamics within the community of editors. Some of these patterns have not been previously explored and carry implications for the knowledge collection practice conducted on Wikipedia. Our method can be applied to other large-scale temporal collaboration networks to identify the existence of negative social interactions and other social processes.

Multiscale Embedded Gene Co-expression Network Analysis

PubMed Central

Song, Won-Min; Zhang, Bin

2015-01-01

Gene co-expression network analysis has been shown effective in identifying functional co-expressed gene modules associated with complex human diseases. However, existing techniques to construct co-expression networks require some critical prior information such as predefined number of clusters, numerical thresholds for defining co-expression/interaction, or do not naturally reproduce the hallmarks of complex systems such as the scale-free degree distribution of small-worldness. Previously, a graph filtering technique called Planar Maximally Filtered Graph (PMFG) has been applied to many real-world data sets such as financial stock prices and gene expression to extract meaningful and relevant interactions. However, PMFG is not suitable for large-scale genomic data due to several drawbacks, such as the high computation complexity O(|V|3), the presence of false-positives due to the maximal planarity constraint, and the inadequacy of the clustering framework. Here, we developed a new co-expression network analysis framework called Multiscale Embedded Gene Co-expression Network Analysis (MEGENA) by: i) introducing quality control of co-expression similarities, ii) parallelizing embedded network construction, and iii) developing a novel clustering technique to identify multi-scale clustering structures in Planar Filtered Networks (PFNs). We applied MEGENA to a series of simulated data and the gene expression data in breast carcinoma and lung adenocarcinoma from The Cancer Genome Atlas (TCGA). MEGENA showed improved performance over well-established clustering methods and co-expression network construction approaches. MEGENA revealed not only meaningful multi-scale organizations of co-expressed gene clusters but also novel targets in breast carcinoma and lung adenocarcinoma. PMID:26618778

Multiscale Embedded Gene Co-expression Network Analysis.

PubMed

Song, Won-Min; Zhang, Bin

2015-11-01

Gene co-expression network analysis has been shown effective in identifying functional co-expressed gene modules associated with complex human diseases. However, existing techniques to construct co-expression networks require some critical prior information such as predefined number of clusters, numerical thresholds for defining co-expression/interaction, or do not naturally reproduce the hallmarks of complex systems such as the scale-free degree distribution of small-worldness. Previously, a graph filtering technique called Planar Maximally Filtered Graph (PMFG) has been applied to many real-world data sets such as financial stock prices and gene expression to extract meaningful and relevant interactions. However, PMFG is not suitable for large-scale genomic data due to several drawbacks, such as the high computation complexity O(|V|3), the presence of false-positives due to the maximal planarity constraint, and the inadequacy of the clustering framework. Here, we developed a new co-expression network analysis framework called Multiscale Embedded Gene Co-expression Network Analysis (MEGENA) by: i) introducing quality control of co-expression similarities, ii) parallelizing embedded network construction, and iii) developing a novel clustering technique to identify multi-scale clustering structures in Planar Filtered Networks (PFNs). We applied MEGENA to a series of simulated data and the gene expression data in breast carcinoma and lung adenocarcinoma from The Cancer Genome Atlas (TCGA). MEGENA showed improved performance over well-established clustering methods and co-expression network construction approaches. MEGENA revealed not only meaningful multi-scale organizations of co-expressed gene clusters but also novel targets in breast carcinoma and lung adenocarcinoma.

Social networks help to infer causality in the tumor microenvironment.

PubMed

Crespo, Isaac; Doucey, Marie-Agnès; Xenarios, Ioannis

2016-03-15

Networks have become a popular way to conceptualize a system of interacting elements, such as electronic circuits, social communication, metabolism or gene regulation. Network inference, analysis, and modeling techniques have been developed in different areas of science and technology, such as computer science, mathematics, physics, and biology, with an active interdisciplinary exchange of concepts and approaches. However, some concepts seem to belong to a specific field without a clear transferability to other domains. At the same time, it is increasingly recognized that within some biological systems--such as the tumor microenvironment--where different types of resident and infiltrating cells interact to carry out their functions, the complexity of the system demands a theoretical framework, such as statistical inference, graph analysis and dynamical models, in order to asses and study the information derived from high-throughput experimental technologies. In this article we propose to adopt and adapt the concepts of influence and investment from the world of social network analysis to biological problems, and in particular to apply this approach to infer causality in the tumor microenvironment. We showed that constructing a bidirectional network of influence between cell and cell communication molecules allowed us to determine the direction of inferred regulations at the expression level and correctly recapitulate cause-effect relationships described in literature. This work constitutes an example of a transfer of knowledge and concepts from the world of social network analysis to biomedical research, in particular to infer network causality in biological networks. This causality elucidation is essential to model the homeostatic response of biological systems to internal and external factors, such as environmental conditions, pathogens or treatments.

“Guilt by Association” Is the Exception Rather Than the Rule in Gene Networks

PubMed Central

Gillis, Jesse; Pavlidis, Paul

2012-01-01

Gene networks are commonly interpreted as encoding functional information in their connections. An extensively validated principle called guilt by association states that genes which are associated or interacting are more likely to share function. Guilt by association provides the central top-down principle for analyzing gene networks in functional terms or assessing their quality in encoding functional information. In this work, we show that functional information within gene networks is typically concentrated in only a very few interactions whose properties cannot be reliably related to the rest of the network. In effect, the apparent encoding of function within networks has been largely driven by outliers whose behaviour cannot even be generalized to individual genes, let alone to the network at large. While experimentalist-driven analysis of interactions may use prior expert knowledge to focus on the small fraction of critically important data, large-scale computational analyses have typically assumed that high-performance cross-validation in a network is due to a generalizable encoding of function. Because we find that gene function is not systemically encoded in networks, but dependent on specific and critical interactions, we conclude it is necessary to focus on the details of how networks encode function and what information computational analyses use to extract functional meaning. We explore a number of consequences of this and find that network structure itself provides clues as to which connections are critical and that systemic properties, such as scale-free-like behaviour, do not map onto the functional connectivity within networks. PMID:22479173

Augmenting Microarray Data with Literature-Based Knowledge to Enhance Gene Regulatory Network Inference

PubMed Central

Kilicoglu, Halil; Shin, Dongwook; Rindflesch, Thomas C.

2014-01-01

Gene regulatory networks are a crucial aspect of systems biology in describing molecular mechanisms of the cell. Various computational models rely on random gene selection to infer such networks from microarray data. While incorporation of prior knowledge into data analysis has been deemed important, in practice, it has generally been limited to referencing genes in probe sets and using curated knowledge bases. We investigate the impact of augmenting microarray data with semantic relations automatically extracted from the literature, with the view that relations encoding gene/protein interactions eliminate the need for random selection of components in non-exhaustive approaches, producing a more accurate model of cellular behavior. A genetic algorithm is then used to optimize the strength of interactions using microarray data and an artificial neural network fitness function. The result is a directed and weighted network providing the individual contribution of each gene to its target. For testing, we used invasive ductile carcinoma of the breast to query the literature and a microarray set containing gene expression changes in these cells over several time points. Our model demonstrates significantly better fitness than the state-of-the-art model, which relies on an initial random selection of genes. Comparison to the component pathways of the KEGG Pathways in Cancer map reveals that the resulting networks contain both known and novel relationships. The p53 pathway results were manually validated in the literature. 60% of non-KEGG relationships were supported (74% for highly weighted interactions). The method was then applied to yeast data and our model again outperformed the comparison model. Our results demonstrate the advantage of combining gene interactions extracted from the literature in the form of semantic relations with microarray analysis in generating contribution-weighted gene regulatory networks. This methodology can make a significant contribution to understanding the complex interactions involved in cellular behavior and molecular physiology. PMID:24921649

Augmenting microarray data with literature-based knowledge to enhance gene regulatory network inference.

PubMed

Chen, Guocai; Cairelli, Michael J; Kilicoglu, Halil; Shin, Dongwook; Rindflesch, Thomas C

2014-06-01

Gene regulatory networks are a crucial aspect of systems biology in describing molecular mechanisms of the cell. Various computational models rely on random gene selection to infer such networks from microarray data. While incorporation of prior knowledge into data analysis has been deemed important, in practice, it has generally been limited to referencing genes in probe sets and using curated knowledge bases. We investigate the impact of augmenting microarray data with semantic relations automatically extracted from the literature, with the view that relations encoding gene/protein interactions eliminate the need for random selection of components in non-exhaustive approaches, producing a more accurate model of cellular behavior. A genetic algorithm is then used to optimize the strength of interactions using microarray data and an artificial neural network fitness function. The result is a directed and weighted network providing the individual contribution of each gene to its target. For testing, we used invasive ductile carcinoma of the breast to query the literature and a microarray set containing gene expression changes in these cells over several time points. Our model demonstrates significantly better fitness than the state-of-the-art model, which relies on an initial random selection of genes. Comparison to the component pathways of the KEGG Pathways in Cancer map reveals that the resulting networks contain both known and novel relationships. The p53 pathway results were manually validated in the literature. 60% of non-KEGG relationships were supported (74% for highly weighted interactions). The method was then applied to yeast data and our model again outperformed the comparison model. Our results demonstrate the advantage of combining gene interactions extracted from the literature in the form of semantic relations with microarray analysis in generating contribution-weighted gene regulatory networks. This methodology can make a significant contribution to understanding the complex interactions involved in cellular behavior and molecular physiology.

VisualCNA: a GUI for interactive constraint network analysis and protein engineering for improving thermostability.

PubMed

Rathi, Prakash Chandra; Mulnaes, Daniel; Gohlke, Holger

2015-07-15

Constraint network analysis (CNA) is a graph theory-based rigidity analysis approach for linking a biomolecule's structure, flexibility, (thermo)stability and function. Results from CNA are highly information-rich and require intuitive, synchronized and interactive visualization for a comprehensive analysis. We developed VisualCNA, an easy-to-use PyMOL plug-in that allows setup of CNA runs and analysis of CNA results linking plots with molecular graphics representations. From a practical viewpoint, the most striking feature of VisualCNA is that it facilitates interactive protein engineering aimed at improving thermostability. VisualCNA and its dependencies (CNA and FIRST software) are available free of charge under GPL and academic licenses, respectively. VisualCNA and CNA are available at http://cpclab.uni-duesseldorf.de/software; FIRST is available at http://flexweb.asu.edu. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Pathway analysis of high-throughput biological data within a Bayesian network framework.

PubMed

Isci, Senol; Ozturk, Cengizhan; Jones, Jon; Otu, Hasan H

2011-06-15

Most current approaches to high-throughput biological data (HTBD) analysis either perform individual gene/protein analysis or, gene/protein set enrichment analysis for a list of biologically relevant molecules. Bayesian Networks (BNs) capture linear and non-linear interactions, handle stochastic events accounting for noise, and focus on local interactions, which can be related to causal inference. Here, we describe for the first time an algorithm that models biological pathways as BNs and identifies pathways that best explain given HTBD by scoring fitness of each network. Proposed method takes into account the connectivity and relatedness between nodes of the pathway through factoring pathway topology in its model. Our simulations using synthetic data demonstrated robustness of our approach. We tested proposed method, Bayesian Pathway Analysis (BPA), on human microarray data regarding renal cell carcinoma (RCC) and compared our results with gene set enrichment analysis. BPA was able to find broader and more specific pathways related to RCC. Accompanying BPA software (BPAS) package is freely available for academic use at http://bumil.boun.edu.tr/bpa.

Advanced functional network analysis in the geosciences: The pyunicorn package

NASA Astrophysics Data System (ADS)

Donges, Jonathan F.; Heitzig, Jobst; Runge, Jakob; Schultz, Hanna C. H.; Wiedermann, Marc; Zech, Alraune; Feldhoff, Jan; Rheinwalt, Aljoscha; Kutza, Hannes; Radebach, Alexander; Marwan, Norbert; Kurths, Jürgen

2013-04-01

Functional networks are a powerful tool for analyzing large geoscientific datasets such as global fields of climate time series originating from observations or model simulations. pyunicorn (pythonic unified complex network and recurrence analysis toolbox) is an open-source, fully object-oriented and easily parallelizable package written in the language Python. It allows for constructing functional networks (aka climate networks) representing the structure of statistical interrelationships in large datasets and, subsequently, investigating this structure using advanced methods of complex network theory such as measures for networks of interacting networks, node-weighted statistics or network surrogates. Additionally, pyunicorn allows to study the complex dynamics of geoscientific systems as recorded by time series by means of recurrence networks and visibility graphs. The range of possible applications of the package is outlined drawing on several examples from climatology.

Gene expression patterns combined with network analysis identify hub genes associated with bladder cancer.

PubMed

Bi, Dongbin; Ning, Hao; Liu, Shuai; Que, Xinxiang; Ding, Kejia

2015-06-01

To explore molecular mechanisms of bladder cancer (BC), network strategy was used to find biomarkers for early detection and diagnosis. The differentially expressed genes (DEGs) between bladder carcinoma patients and normal subjects were screened using empirical Bayes method of the linear models for microarray data package. Co-expression networks were constructed by differentially co-expressed genes and links. Regulatory impact factors (RIF) metric was used to identify critical transcription factors (TFs). The protein-protein interaction (PPI) networks were constructed by the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and clusters were obtained through molecular complex detection (MCODE) algorithm. Centralities analyses for complex networks were performed based on degree, stress and betweenness. Enrichment analyses were performed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Co-expression networks and TFs (based on expression data of global DEGs and DEGs in different stages and grades) were identified. Hub genes of complex networks, such as UBE2C, ACTA2, FABP4, CKS2, FN1 and TOP2A, were also obtained according to analysis of degree. In gene enrichment analyses of global DEGs, cell adhesion, proteinaceous extracellular matrix and extracellular matrix structural constituent were top three GO terms. ECM-receptor interaction, focal adhesion, and cell cycle were significant pathways. Our results provide some potential underlying biomarkers of BC. However, further validation is required and deep studies are needed to elucidate the pathogenesis of BC. Copyright © 2015 Elsevier Ltd. All rights reserved.

Health and disease phenotyping in old age using a cluster network analysis.

PubMed

Valenzuela, Jesus Felix; Monterola, Christopher; Tong, Victor Joo Chuan; Ng, Tze Pin; Larbi, Anis

2017-11-15

Human ageing is a complex trait that involves the synergistic action of numerous biological processes that interact to form a complex network. Here we performed a network analysis to examine the interrelationships between physiological and psychological functions, disease, disability, quality of life, lifestyle and behavioural risk factors for ageing in a cohort of 3,270 subjects aged ≥55 years. We considered associations between numerical and categorical descriptors using effect-size measures for each variable pair and identified clusters of variables from the resulting pairwise effect-size network and minimum spanning tree. We show, by way of a correspondence analysis between the two sets of clusters, that they correspond to coarse-grained and fine-grained structure of the network relationships. The clusters obtained from the minimum spanning tree mapped to various conceptual domains and corresponded to physiological and syndromic states. Hierarchical ordering of these clusters identified six common themes based on interactions with physiological systems and common underlying substrates of age-associated morbidity and disease chronicity, functional disability, and quality of life. These findings provide a starting point for indepth analyses of ageing that incorporate immunologic, metabolomic and proteomic biomarkers, and ultimately offer low-level-based typologies of healthy and unhealthy ageing.

Network analysis of a regional fishery: Implications for management of natural resources, and recruitment and retention of anglers

USGS Publications Warehouse

Martin, Dustin R.; Shizuka, Daizaburo; Chizinski, Christopher J.; Pope, Kevin L.

2017-01-01

Angler groups and water-body types interact to create a complex social-ecological system. Network analysis could inform detailed mechanistic models on, and provide managers better information about, basic patterns of fishing activity. Differences in behavior and reservoir selection among angler groups in a regional fishery, the Salt Valley fishery in southeastern Nebraska, USA, were assessed using a combination of cluster and network analyses. The four angler groups assessed ranged from less active, unskilled anglers (group One) to highly active, very skilled anglers (group Four). Reservoir use patterns and the resulting network communities of these four angler groups differed; the number of reservoir communities for these groups ranged from two to three and appeared to be driven by reservoir location (group One), reservoir size and its associated attributes (groups Two and Four), or an interaction between reservoir size and location (group Three). Network analysis is a useful tool to describe differences in participation among angler groups within a regional fishery, and provides new insights about possible recruitment of anglers. For example, group One anglers fished reservoirs closer to home and had a greater probability of dropping out if local reservoir access were restricted.

Social traits, social networks and evolutionary biology.

PubMed

Fisher, D N; McAdam, A G

2017-12-01

The social environment is both an important agent of selection for most organisms, and an emergent property of their interactions. As an aggregation of interactions among members of a population, the social environment is a product of many sets of relationships and so can be represented as a network or matrix. Social network analysis in animals has focused on why these networks possess the structure they do, and whether individuals' network traits, representing some aspect of their social phenotype, relate to their fitness. Meanwhile, quantitative geneticists have demonstrated that traits expressed in a social context can depend on the phenotypes and genotypes of interacting partners, leading to influences of the social environment on the traits and fitness of individuals and the evolutionary trajectories of populations. Therefore, both fields are investigating similar topics, yet have arrived at these points relatively independently. We review how these approaches are diverged, and yet how they retain clear parallelism and so strong potential for complementarity. This demonstrates that, despite separate bodies of theory, advances in one might inform the other. Techniques in network analysis for quantifying social phenotypes, and for identifying community structure, should be useful for those studying the relationship between individual behaviour and group-level phenotypes. Entering social association matrices into quantitative genetic models may also reduce bias in heritability estimates, and allow the estimation of the influence of social connectedness on trait expression. Current methods for measuring natural selection in a social context explicitly account for the fact that a trait is not necessarily the property of a single individual, something the network approaches have not yet considered when relating network metrics to individual fitness. Harnessing evolutionary models that consider traits affected by genes in other individuals (i.e. indirect genetic effects) provides the potential to understand how entire networks of social interactions in populations influence phenotypes and predict how these traits may evolve. By theoretical integration of social network analysis and quantitative genetics, we hope to identify areas of compatibility and incompatibility and to direct research efforts towards the most promising areas. Continuing this synthesis could provide important insights into the evolution of traits expressed in a social context and the evolutionary consequences of complex and nuanced social phenotypes. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

On the molecular origins of biomass recalcitrance: the interaction network and solvation structures of cellulose microfibrils.

PubMed

Gross, Adam S; Chu, Jhih-Wei

2010-10-28

Biomass recalcitrance is a fundamental bottleneck to producing fuels from renewable sources. To understand its molecular origin, we characterize the interaction network and solvation structures of cellulose microfibrils via all-atom molecular dynamics simulations. The network is divided into three components: intrachain, interchain, and intersheet interactions. Analysis of their spatial dependence and interaction energetics indicate that intersheet interactions are the most robust and strongest component and do not display a noticeable dependence on solvent exposure. Conversely, the strength of surface-exposed intrachain and interchain hydrogen bonds is significantly reduced. Comparing the interaction networks of I(β) and I(α) cellulose also shows that the number of intersheet interactions is a clear descriptor that distinguishes the two allomorphs and is consistent with the observation that I(β) is the more stable form. These results highlight the dominant role of the often-overlooked intersheet interactions in giving rise to biomass recalcitrance. We also analyze the solvation structures around the surfaces of microfibrils and show that the structural and chemical features at cellulose surfaces constrict water molecules into specific density profiles and pair correlation functions. Calculations of water density and compressibility in the hydration shell show noticeable but not drastic differences. Therefore, specific solvation structures are more prominent signatures of different surfaces.

Investigation on Law and Economics Based on Complex Network and Time Series Analysis.

PubMed

Yang, Jian; Qu, Zhao; Chang, Hui

2015-01-01

The research focuses on the cooperative relationship and the strategy tendency among three mutually interactive parties in financing: small enterprises, commercial banks and micro-credit companies. Complex network theory and time series analysis were applied to figure out the quantitative evidence. Moreover, this paper built up a fundamental model describing the particular interaction among them through evolutionary game. Combining the results of data analysis and current situation, it is justifiable to put forward reasonable legislative recommendations for regulations on lending activities among small enterprises, commercial banks and micro-credit companies. The approach in this research provides a framework for constructing mathematical models and applying econometrics and evolutionary game in the issue of corporation financing.

Aligning Biomolecular Networks Using Modular Graph Kernels

NASA Astrophysics Data System (ADS)

Towfic, Fadi; Greenlee, M. Heather West; Honavar, Vasant

Comparative analysis of biomolecular networks constructed using measurements from different conditions, tissues, and organisms offer a powerful approach to understanding the structure, function, dynamics, and evolution of complex biological systems. We explore a class of algorithms for aligning large biomolecular networks by breaking down such networks into subgraphs and computing the alignment of the networks based on the alignment of their subgraphs. The resulting subnetworks are compared using graph kernels as scoring functions. We provide implementations of the resulting algorithms as part of BiNA, an open source biomolecular network alignment toolkit. Our experiments using Drosophila melanogaster, Saccharomyces cerevisiae, Mus musculus and Homo sapiens protein-protein interaction networks extracted from the DIP repository of protein-protein interaction data demonstrate that the performance of the proposed algorithms (as measured by % GO term enrichment of subnetworks identified by the alignment) is competitive with some of the state-of-the-art algorithms for pair-wise alignment of large protein-protein interaction networks. Our results also show that the inter-species similarity scores computed based on graph kernels can be used to cluster the species into a species tree that is consistent with the known phylogenetic relationships among the species.

Social disadvantage and borderline personality disorder: A study of social networks.

PubMed

Beeney, Joseph E; Hallquist, Michael N; Clifton, Allan D; Lazarus, Sophie A; Pilkonis, Paul A

2018-01-01

Examining differences in social integration, social support, and relationship characteristics in social networks may be critical for understanding the character and costs of the social difficulties experienced of borderline personality disorder (BPD). We conducted an ego-based (self-reported, individual) social network analysis of 142 participants recruited from clinical and community sources. Each participant listed the 30 most significant people (called alters) in their social network, then rated each alter in terms of amount of contact, social support, attachment strength and negative interactions. In addition, measures of social integration were determined using participant's report of the connection between people in their networks. BPD was associated with poorer social support, more frequent negative interactions, and less social integration. Examination of alter-by-BPD interactions indicated that whereas participants with low BPD symptoms had close relationships with people with high centrality within their networks, participants with high BPD symptoms had their closest relationships with people less central to their networks. The results suggest that individuals with BPD are at a social disadvantage: Those with whom they are most closely linked (including romantic partners) are less socially connected (i.e., less central) within their social network. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Network pharmacology-based prediction of active compounds and molecular targets in Yijin-Tang acting on hyperlipidaemia and atherosclerosis.

PubMed

Lee, A Yeong; Park, Won; Kang, Tae-Wook; Cha, Min Ho; Chun, Jin Mi

2018-07-15

Yijin-Tang (YJT) is a traditional prescription for the treatment of hyperlipidaemia, atherosclerosis and other ailments related to dampness phlegm, a typical pathological symptom of abnormal body fluid metabolism in Traditional Korean Medicine. However, a holistic network pharmacology approach to understanding the therapeutic mechanisms underlying hyperlipidaemia and atherosclerosis has not been pursued. To examine the network pharmacological potential effects of YJT on hyperlipidaemia and atherosclerosis, we analysed components, performed target prediction and network analysis, and investigated interacting pathways using a network pharmacology approach. Information on compounds in herbal medicines was obtained from public databases, and oral bioavailability and drug-likeness was screened using absorption, distribution, metabolism, and excretion (ADME) criteria. Correlations between compounds and genes were linked using the STITCH database, and genes related to hyperlipidaemia and atherosclerosis were gathered using the GeneCards database. Human genes were identified and subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Network analysis identified 447 compounds in five herbal medicines that were subjected to ADME screening, and 21 compounds and 57 genes formed the main pathways linked to hyperlipidaemia and atherosclerosis. Among them, 10 compounds (naringenin, nobiletin, hesperidin, galangin, glycyrrhizin, homogentisic acid, stigmasterol, 6-gingerol, quercetin and glabridin) were linked to more than four genes, and are bioactive compounds and key chemicals. Core genes in this network were CASP3, CYP1A1, CYP1A2, MMP2 and MMP9. The compound-target gene network revealed close interactions between multiple components and multiple targets, and facilitates a better understanding of the potential therapeutic effects of YJT. Pharmacological network analysis can help to explain the potential effects of YJT for treating dampness phlegm-related diseases such as hyperlipidaemia and atherosclerosis. Copyright © 2018 Elsevier B.V. All rights reserved.

CoryneRegNet 4.0 – A reference database for corynebacterial gene regulatory networks

PubMed Central

Baumbach, Jan

2007-01-01

Background Detailed information on DNA-binding transcription factors (the key players in the regulation of gene expression) and on transcriptional regulatory interactions of microorganisms deduced from literature-derived knowledge, computer predictions and global DNA microarray hybridization experiments, has opened the way for the genome-wide analysis of transcriptional regulatory networks. The large-scale reconstruction of these networks allows the in silico analysis of cell behavior in response to changing environmental conditions. We previously published CoryneRegNet, an ontology-based data warehouse of corynebacterial transcription factors and regulatory networks. Initially, it was designed to provide methods for the analysis and visualization of the gene regulatory network of Corynebacterium glutamicum. Results Now we introduce CoryneRegNet release 4.0, which integrates data on the gene regulatory networks of 4 corynebacteria, 2 mycobacteria and the model organism Escherichia coli K12. As the previous versions, CoryneRegNet provides a web-based user interface to access the database content, to allow various queries, and to support the reconstruction, analysis and visualization of regulatory networks at different hierarchical levels. In this article, we present the further improved database content of CoryneRegNet along with novel analysis features. The network visualization feature GraphVis now allows the inter-species comparisons of reconstructed gene regulatory networks and the projection of gene expression levels onto that networks. Therefore, we added stimulon data directly into the database, but also provide Web Service access to the DNA microarray analysis platform EMMA. Additionally, CoryneRegNet now provides a SOAP based Web Service server, which can easily be consumed by other bioinformatics software systems. Stimulons (imported from the database, or uploaded by the user) can be analyzed in the context of known transcriptional regulatory networks to predict putative contradictions or further gene regulatory interactions. Furthermore, it integrates protein clusters by means of heuristically solving the weighted graph cluster editing problem. In addition, it provides Web Service based access to up to date gene annotation data from GenDB. Conclusion The release 4.0 of CoryneRegNet is a comprehensive system for the integrated analysis of procaryotic gene regulatory networks. It is a versatile systems biology platform to support the efficient and large-scale analysis of transcriptional regulation of gene expression in microorganisms. It is publicly available at . PMID:17986320

Linear time-varying models can reveal non-linear interactions of biomolecular regulatory networks using multiple time-series data.

PubMed

Kim, Jongrae; Bates, Declan G; Postlethwaite, Ian; Heslop-Harrison, Pat; Cho, Kwang-Hyun

2008-05-15

Inherent non-linearities in biomolecular interactions make the identification of network interactions difficult. One of the principal problems is that all methods based on the use of linear time-invariant models will have fundamental limitations in their capability to infer certain non-linear network interactions. Another difficulty is the multiplicity of possible solutions, since, for a given dataset, there may be many different possible networks which generate the same time-series expression profiles. A novel algorithm for the inference of biomolecular interaction networks from temporal expression data is presented. Linear time-varying models, which can represent a much wider class of time-series data than linear time-invariant models, are employed in the algorithm. From time-series expression profiles, the model parameters are identified by solving a non-linear optimization problem. In order to systematically reduce the set of possible solutions for the optimization problem, a filtering process is performed using a phase-portrait analysis with random numerical perturbations. The proposed approach has the advantages of not requiring the system to be in a stable steady state, of using time-series profiles which have been generated by a single experiment, and of allowing non-linear network interactions to be identified. The ability of the proposed algorithm to correctly infer network interactions is illustrated by its application to three examples: a non-linear model for cAMP oscillations in Dictyostelium discoideum, the cell-cycle data for Saccharomyces cerevisiae and a large-scale non-linear model of a group of synchronized Dictyostelium cells. The software used in this article is available from http://sbie.kaist.ac.kr/software

Long-range functional interactions of anterior insula and medial frontal cortex are differently modulated by visuospatial and inductive reasoning tasks.

PubMed

Ebisch, Sjoerd J H; Mantini, Dante; Romanelli, Roberta; Tommasi, Marco; Perrucci, Mauro G; Romani, Gian Luca; Colom, Roberto; Saggino, Aristide

2013-09-01

The brain is organized into functionally specific networks as characterized by intrinsic functional relationships within discrete sets of brain regions. However, it is poorly understood whether such functional networks are dynamically organized according to specific task-states. The anterior insular cortex (aIC)-dorsal anterior cingulate cortex (dACC)/medial frontal cortex (mFC) network has been proposed to play a central role in human cognitive abilities. The present functional magnetic resonance imaging (fMRI) study aimed at testing whether functional interactions of the aIC-dACC/mFC network in terms of temporally correlated patterns of neural activity across brain regions are dynamically modulated by transitory, ongoing task demands. For this purpose, functional interactions of the aIC-dACC/mFC network are compared during two distinguishable fluid reasoning tasks, Visualization and Induction. The results show an increased functional coupling of bilateral aIC with visual cortices in the occipital lobe during the Visualization task, whereas coupling of mFC with right anterior frontal cortex was enhanced during the Induction task. These task-specific modulations of functional interactions likely reflect ability related neural processing. Furthermore, functional connectivity strength between right aIC and right dACC/mFC reliably predicts general task performance. The findings suggest that the analysis of long-range functional interactions may provide complementary information about brain-behavior relationships. On the basis of our results, it is proposed that the aIC-dACC/mFC network contributes to the integration of task-common and task-specific information based on its within-network as well as its between-network dynamic functional interactions. Copyright © 2013 Elsevier Inc. All rights reserved.

Electrical circuit modeling and analysis of microwave acoustic interaction with biological tissues.

PubMed

Gao, Fei; Zheng, Qian; Zheng, Yuanjin

2014-05-01

Numerical study of microwave imaging and microwave-induced thermoacoustic imaging utilizes finite difference time domain (FDTD) analysis for simulation of microwave and acoustic interaction with biological tissues, which is time consuming due to complex grid-segmentation and numerous calculations, not straightforward due to no analytical solution and physical explanation, and incompatible with hardware development requiring circuit simulator such as SPICE. In this paper, instead of conventional FDTD numerical simulation, an equivalent electrical circuit model is proposed to model the microwave acoustic interaction with biological tissues for fast simulation and quantitative analysis in both one and two dimensions (2D). The equivalent circuit of ideal point-like tissue for microwave-acoustic interaction is proposed including transmission line, voltage-controlled current source, envelop detector, and resistor-inductor-capacitor (RLC) network, to model the microwave scattering, thermal expansion, and acoustic generation. Based on which, two-port network of the point-like tissue is built and characterized using pseudo S-parameters and transducer gain. Two dimensional circuit network including acoustic scatterer and acoustic channel is also constructed to model the 2D spatial information and acoustic scattering effect in heterogeneous medium. Both FDTD simulation, circuit simulation, and experimental measurement are performed to compare the results in terms of time domain, frequency domain, and pseudo S-parameters characterization. 2D circuit network simulation is also performed under different scenarios including different sizes of tumors and the effect of acoustic scatterer. The proposed circuit model of microwave acoustic interaction with biological tissue could give good agreement with FDTD simulated and experimental measured results. The pseudo S-parameters and characteristic gain could globally evaluate the performance of tumor detection. The 2D circuit network enables the potential to combine the quasi-numerical simulation and circuit simulation in a uniform simulator for codesign and simulation of a microwave acoustic imaging system, bridging bioeffect study and hardware development seamlessly.

Real-time scalable visual analysis on mobile devices

NASA Astrophysics Data System (ADS)

Pattath, Avin; Ebert, David S.; May, Richard A.; Collins, Timothy F.; Pike, William

2008-02-01

Interactive visual presentation of information can help an analyst gain faster and better insight from data. When combined with situational or context information, visualization on mobile devices is invaluable to in-field responders and investigators. However, several challenges are posed by the form-factor of mobile devices in developing such systems. In this paper, we classify these challenges into two broad categories - issues in general mobile computing and issues specific to visual analysis on mobile devices. Using NetworkVis and Infostar as example systems, we illustrate some of the techniques that we employed to overcome many of the identified challenges. NetworkVis is an OpenVG-based real-time network monitoring and visualization system developed for Windows Mobile devices. Infostar is a flash-based interactive, real-time visualization application intended to provide attendees access to conference information. Linked time-synchronous visualization, stylus/button-based interactivity, vector graphics, overview-context techniques, details-on-demand and statistical information display are some of the highlights of these applications.

Atopic dermatitis-associated protein interaction network lead to new insights in chronic sulfur mustard skin lesion mechanisms.

PubMed

Amiri, Mojtaba; Jafari, Mohieddin; Azimzadeh Jamalkandi, Sadegh; Davoodi, Seyed-Masoud

2013-10-01

Chronic sulfur mustard skin lesions (CSMSLs) are the most common complications of sulfur mustard exposure; however, its mechanism is not completely understood.According to clinical signs, there are similarities between CSMSL and atopic dermatitis (AD). In this study, proteomic results of AD were reviewed and the AD-associated protein-protein interaction network (PIN) was analyzed. According to centrality measurements, 16 proteins were designated as pivotal elements in AD mechanisms. Interestingly, most of these proteins had been reported in some sulfur mustard-related studies in late and acute phases separately. Based on the gene enrichment analysis, aging, cell response to stress, cancer, Toll- and NOD-like receptor and apoptosis signaling pathways have the greatest impact on the disease. By the analysis of directed protein interaction networks, it is concluded that TNF, IL-6, AKT1, NOS3 and CDKN1A are the most important proteins. It is possible that these proteins play role in the shared complications of AD and CSMSL including xerosis and itching.

Chinese EFL Teachers' Social Interaction and Socio-Cognitive Presence in Synchronous Computer-Mediated Communication

ERIC Educational Resources Information Center

Wu, Heping; Gao, Junde; Zhang, Weimin

2014-01-01

The present study examines the professional growth of three Chinese English teachers by analyzing their interactional patterns and their social and cognitive presence in an online community. The data from social network analysis (SNA) and content analysis revealed that computer-mediated communication (CMC) created new opportunities for teachers to…

MOVANAID: An Interactive Aid for Analysis of Movement Capabilities.

ERIC Educational Resources Information Center

Cooper, George E.; And Others

A computer-drive interactive aid for movement analysis, called MOVANAID, has been developed to be of assistance in the performance of certain Army intelligence processing tasks in a tactical environment. It can compute fastest travel times and paths through road networks for military units of various types, as well as fastest times in which…

Predicting community responses to perturbations in the face of imperfect knowledge and network complexity

USGS Publications Warehouse

Novak, M.; Wootton, J.T.; Doak, D.F.; Emmerson, M.; Estes, J.A.; Tinker, M.T.

2011-01-01

How best to predict the effects of perturbations to ecological communities has been a long-standing goal for both applied and basic ecology. This quest has recently been revived by new empirical data, new analysis methods, and increased computing speed, with the promise that ecologically important insights may be obtainable from a limited knowledge of community interactions. We use empirically based and simulated networks of varying size and connectance to assess two limitations to predicting perturbation responses in multispecies communities: (1) the inaccuracy by which species interaction strengths are empirically quantified and (2) the indeterminacy of species responses due to indirect effects associated with network size and structure. We find that even modest levels of species richness and connectance (??25 pairwise interactions) impose high requirements for interaction strength estimates because system indeterminacy rapidly overwhelms predictive insights. Nevertheless, even poorly estimated interaction strengths provide greater average predictive certainty than an approach that uses only the sign of each interaction. Our simulations provide guidance in dealing with the trade-offs involved in maximizing the utility of network approaches for predicting dynamics in multispecies communities. ?? 2011 by the Ecological Society of America.

Mother's Social Network and Family Language Maintenance

ERIC Educational Resources Information Center

Velazquez, Isabel

2013-01-01

This article reports the results of a social network analysis (SNA) performed on the mother's primary network of interaction in 15 Mexican American families in the city of El Paso, Texas, the neighbourhood of La Villita, in Chicago, and the city of Lincoln, Nebraska. The goal of this study was to examine potential opportunities for Spanish use by…

Evidence for Functional Networks within the Human Brain's White Matter.

PubMed

Peer, Michael; Nitzan, Mor; Bick, Atira S; Levin, Netta; Arzy, Shahar

2017-07-05

Investigation of the functional macro-scale organization of the human cortex is fundamental in modern neuroscience. Although numerous studies have identified networks of interacting functional modules in the gray-matter, limited research was directed to the functional organization of the white-matter. Recent studies have demonstrated that the white-matter exhibits blood oxygen level-dependent signal fluctuations similar to those of the gray-matter. Here we used these signal fluctuations to investigate whether the white-matter is organized as functional networks by applying a clustering analysis on resting-state functional MRI (RSfMRI) data from white-matter voxels, in 176 subjects (of both sexes). This analysis indicated the existence of 12 symmetrical white-matter functional networks, corresponding to combinations of white-matter tracts identified by diffusion tensor imaging. Six of the networks included interhemispheric commissural bridges traversing the corpus callosum. Signals in white-matter networks correlated with signals from functional gray-matter networks, providing missing knowledge on how these distributed networks communicate across large distances. These findings were replicated in an independent subject group and were corroborated by seed-based analysis in small groups and individual subjects. The identified white-matter functional atlases and analysis codes are available at http://mind.huji.ac.il/white-matter.aspx Our results demonstrate that the white-matter manifests an intrinsic functional organization as interacting networks of functional modules, similarly to the gray-matter, which can be investigated using RSfMRI. The discovery of functional networks within the white-matter may open new avenues of research in cognitive neuroscience and clinical neuropsychiatry. SIGNIFICANCE STATEMENT In recent years, functional MRI (fMRI) has revolutionized all fields of neuroscience, enabling identifications of functional modules and networks in the human brain. However, most fMRI studies ignored a major part of the brain, the white-matter, discarding signals from it as arising from noise. Here we use resting-state fMRI data from 176 subjects to show that signals from the human white-matter contain meaningful information. We identify 12 functional networks composed of interacting long-distance white-matter tracts. Moreover, we show that these networks are highly correlated to resting-state gray-matter networks, highlighting their functional role. Our findings enable reinterpretation of many existing fMRI datasets, and suggest a new way to explore the white-matter role in cognition and its disturbances in neuropsychiatric disorders. Copyright © 2017 the authors 0270-6474/17/376394-14$15.00/0.

Interaction of multiple networks modulated by the working memory training based on real-time fMRI

NASA Astrophysics Data System (ADS)

Shen, Jiahui; Zhang, Gaoyan; Zhu, Chaozhe; Yao, Li; Zhao, Xiaojie

2015-03-01

Neuroimaging studies of working memory training have identified the alteration of brain activity as well as the regional interactions within the functional networks such as central executive network (CEN) and default mode network (DMN). However, how the interaction within and between these multiple networks is modulated by the training remains unclear. In this paper, we examined the interaction of three training-induced brain networks during working memory training based on real-time functional magnetic resonance imaging (rtfMRI). Thirty subjects assigned to the experimental and control group respectively participated in two times training separated by seven days. Three networks including silence network (SN), CEN and DMN were identified by the training data with the calculated function connections within each network. Structural equation modeling (SEM) approach was used to construct the directional connectivity patterns. The results showed that the causal influences from the percent signal changes of target ROI to the SN were positively changed in both two groups, as well as the causal influence from the SN to CEN was positively changed in experimental group but negatively changed in control group from the SN to DMN. Further correlation analysis of the changes in each network with the behavioral improvements showed that the changes in SN were stronger positively correlated with the behavioral improvement of letter memory task. These findings indicated that the SN was not only a switch between the target ROI and the other networks in the feedback training but also an essential factor to the behavioral improvement.

Instantaneous and causal connectivity in resting state brain networks derived from functional MRI data.

PubMed

Deshpande, Gopikrishna; Santhanam, Priya; Hu, Xiaoping

2011-01-15

Most neuroimaging studies of resting state networks have concentrated on functional connectivity (FC) based on instantaneous correlation in a single network. In this study we investigated both FC and effective connectivity (EC) based on Granger causality of four important networks at resting state derived from functional magnetic resonance imaging data - default mode network (DMN), hippocampal cortical memory network (HCMN), dorsal attention network (DAN) and fronto-parietal control network (FPCN). A method called correlation-purged Granger causality analysis was used, not only enabling the simultaneous evaluation of FC and EC of all networks using a single multivariate model, but also accounting for the interaction between them resulting from the smoothing of neuronal activity by hemodynamics. FC was visualized using a force-directed layout upon which causal interactions were overlaid. FC results revealed that DAN is very tightly coupled compared to the other networks while the DMN forms the backbone around which the other networks amalgamate. The pattern of bidirectional causal interactions indicates that posterior cingulate and posterior inferior parietal lobule of DMN act as major hubs. The pattern of unidirectional causal paths revealed that hippocampus and anterior prefrontal cortex (aPFC) receive major inputs, likely reflecting memory encoding/retrieval and cognitive integration, respectively. Major outputs emanating from anterior insula and middle temporal area, which are directed at aPFC, may carry information about interoceptive awareness and external environment, respectively, into aPFC for integration, supporting the hypothesis that aPFC-seeded FPCN acts as a control network. Our findings indicate the following. First, regions whose activities are not synchronized interact via time-delayed causal influences. Second, the causal interactions are organized such that cingulo-parietal regions act as hubs. Finally, segregation of different resting state networks is not clear cut but only by soft boundaries. Copyright © 2010 Elsevier Inc. All rights reserved.

Orthoscape: a cytoscape application for grouping and visualization KEGG based gene networks by taxonomy and homology principles.

PubMed

Mustafin, Zakhar Sergeevich; Lashin, Sergey Alexandrovich; Matushkin, Yury Georgievich; Gunbin, Konstantin Vladimirovich; Afonnikov, Dmitry Arkadievich

2017-01-27

There are many available software tools for visualization and analysis of biological networks. Among them, Cytoscape ( http://cytoscape.org/ ) is one of the most comprehensive packages, with many plugins and applications which extends its functionality by providing analysis of protein-protein interaction, gene regulatory and gene co-expression networks, metabolic, signaling, neural as well as ecological-type networks including food webs, communities networks etc. Nevertheless, only three plugins tagged 'network evolution' found in Cytoscape official app store and in literature. We have developed a new Cytoscape 3.0 application Orthoscape aimed to facilitate evolutionary analysis of gene networks and visualize the results. Orthoscape aids in analysis of evolutionary information available for gene sets and networks by highlighting: (1) the orthology relationships between genes; (2) the evolutionary origin of gene network components; (3) the evolutionary pressure mode (diversifying or stabilizing, negative or positive selection) of orthologous groups in general and/or branch-oriented mode. The distinctive feature of Orthoscape is the ability to control all data analysis steps via user-friendly interface. Orthoscape allows its users to analyze gene networks or separated gene sets in the context of evolution. At each step of data analysis, Orthoscape also provides for convenient visualization and data manipulation.

Exploring Peer Relationships, Friendships and Group Work Dynamics in Higher Education: Applying Social Network Analysis

ERIC Educational Resources Information Center

Mamas, Christoforos

2018-01-01

This study primarily applied social network analysis (SNA) to explore the relationship between friendships, peer social interactions and group work dynamics within a higher education undergraduate programme in England. A critical case study design was adopted so as to allow for an in-depth exploration of the students' voice. In doing so, the views…

Visualization Techniques for Computer Network Defense

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beaver, Justin M; Steed, Chad A; Patton, Robert M

2011-01-01

Effective visual analysis of computer network defense (CND) information is challenging due to the volume and complexity of both the raw and analyzed network data. A typical CND is comprised of multiple niche intrusion detection tools, each of which performs network data analysis and produces a unique alerting output. The state-of-the-practice in the situational awareness of CND data is the prevalent use of custom-developed scripts by Information Technology (IT) professionals to retrieve, organize, and understand potential threat events. We propose a new visual analytics framework, called the Oak Ridge Cyber Analytics (ORCA) system, for CND data that allows an operatormore » to interact with all detection tool outputs simultaneously. Aggregated alert events are presented in multiple coordinated views with timeline, cluster, and swarm model analysis displays. These displays are complemented with both supervised and semi-supervised machine learning classifiers. The intent of the visual analytics framework is to improve CND situational awareness, to enable an analyst to quickly navigate and analyze thousands of detected events, and to combine sophisticated data analysis techniques with interactive visualization such that patterns of anomalous activities may be more easily identified and investigated.« less

Integrating network ecology with applied conservation: a synthesis and guide to implementation.

PubMed

Kaiser-Bunbury, Christopher N; Blüthgen, Nico

2015-07-10

Ecological networks are a useful tool to study the complexity of biotic interactions at a community level. Advances in the understanding of network patterns encourage the application of a network approach in other disciplines than theoretical ecology, such as biodiversity conservation. So far, however, practical applications have been meagre. Here we present a framework for network analysis to be harnessed to advance conservation management by using plant-pollinator networks and islands as model systems. Conservation practitioners require indicators to monitor and assess management effectiveness and validate overall conservation goals. By distinguishing between two network attributes, the 'diversity' and 'distribution' of interactions, on three hierarchical levels (species, guild/group and network) we identify seven quantitative metrics to describe changes in network patterns that have implications for conservation. Diversity metrics are partner diversity, vulnerability/generality, interaction diversity and interaction evenness, and distribution metrics are the specialization indices d' and [Formula: see text] and modularity. Distribution metrics account for sampling bias and may therefore be suitable indicators to detect human-induced changes to plant-pollinator communities, thus indirectly assessing the structural and functional robustness and integrity of ecosystems. We propose an implementation pathway that outlines the stages that are required to successfully embed a network approach in biodiversity conservation. Most importantly, only if conservation action and study design are aligned by practitioners and ecologists through joint experiments, are the findings of a conservation network approach equally beneficial for advancing adaptive management and ecological network theory. We list potential obstacles to the framework, highlight the shortfall in empirical, mostly experimental, network data and discuss possible solutions. Published by Oxford University Press on behalf of the Annals of Botany Company.

Comprehensive Analysis of Interaction Networks of Telomerase Reverse Transcriptase with Multiple Bioinformatic Approaches: Deep Mining the Potential Functions of Telomere and Telomerase.

PubMed

Hou, Chunyu; Wang, Fei; Liu, Xuewen; Chang, Guangming; Wang, Feng; Geng, Xin

2017-08-01

Telomerase reverse transcriptase (TERT) is the protein component of telomerase complex. Evidence has accumulated showing that the nontelomeric functions of TERT are independent of telomere elongation. However, the mechanisms governing the interaction between TERT and its target genes are not clearly revealed. The biological functions of TERT are not fully elucidated and have thus far been underestimated. To further explore these functions, we investigated TERT interaction networks using multiple bioinformatic databases, including BioGRID, STRING, DAVID, GeneCards, GeneMANIA, PANTHER, miRWalk, mirTarBase, miRNet, miRDB, and TargetScan. In addition, network diagrams were built using Cytoscape software. As competing endogenous RNAs (ceRNAs) are endogenous transcripts that compete for the binding of microRNAs (miRNAs) by using shared miRNA recognition elements, they are involved in creating widespread regulatory networks. Therefore, the ceRNA regulatory networks of TERT were also investigated in this study. Interestingly, we found that the three genes PABPC1, SLC7A11, and TP53 were present in both TERT interaction networks and ceRNAs target genes. It was predicted that TERT might play nontelomeric roles in the generation or development of some rare diseases, such as Rift Valley fever and dyscalculia. Thus, our data will help to decipher the interaction networks of TERT and reveal the unknown functions of telomerase in cancer and aging-related diseases.

Differential reward responses during competition against in- and out-of-network others.

PubMed

Fareri, Dominic S; Delgado, Mauricio R

2014-04-01

Social interactions occur within a variety of different contexts--cooperative/competitive--and often involve members of our social network. Here, we investigated whether social network modulated the value placed on positive outcomes during a competitive context. Eighteen human participants played a simple card-guessing game with three different competitors: a close friend (in-network), a confederate (out-of-network) and a random number generator (non-social condition) while undergoing functional magnetic resonance imaging. Neuroimaging results at the time of outcome receipt demonstrated a significant main effect of competitor across multiple regions of medial prefrontal cortex, with Blood Oxygen Level Dependent (BOLD) responses strongest when competing against one's friend compared with all other conditions. Striatal BOLD responses demonstrated a more general sensitivity to positive compared with negative monetary outcomes, which an exploratory analysis revealed to be stronger when interacting with social, compared with non-social, competitors. Interestingly, a Granger causality analysis indicated directed influences sent from an medial prefrontal cortex (mPFC) region, which shows social network differentiation of outcomes, and the ventral striatum bilaterally. Our results suggest that when competing against others of varying degrees of social network, mPFC differentially values these outcomes, perhaps treating in-network outcomes as more informative, leaving the striatum to more general value computations.

Differential reward responses during competition against in- and out-of-network others

PubMed Central

Fareri, Dominic S.

2014-01-01

Social interactions occur within a variety of different contexts––cooperative/competitive––and often involve members of our social network. Here, we investigated whether social network modulated the value placed on positive outcomes during a competitive context. Eighteen human participants played a simple card-guessing game with three different competitors: a close friend (in-network), a confederate (out-of-network) and a random number generator (non-social condition) while undergoing functional magnetic resonance imaging. Neuroimaging results at the time of outcome receipt demonstrated a significant main effect of competitor across multiple regions of medial prefrontal cortex, with Blood Oxygen Level Dependent (BOLD) responses strongest when competing against one’s friend compared with all other conditions. Striatal BOLD responses demonstrated a more general sensitivity to positive compared with negative monetary outcomes, which an exploratory analysis revealed to be stronger when interacting with social, compared with non-social, competitors. Interestingly, a Granger causality analysis indicated directed influences sent from an medial prefrontal cortex (mPFC) region, which shows social network differentiation of outcomes, and the ventral striatum bilaterally. Our results suggest that when competing against others of varying degrees of social network, mPFC differentially values these outcomes, perhaps treating in-network outcomes as more informative, leaving the striatum to more general value computations. PMID:23314007

Dengue-2 structural proteins associate with human proteins to produce a coagulation and innate immune response biased interactome.

PubMed

Folly, Brenda B; Weffort-Santos, Almeriane M; Fathman, C G; Soares, Luis R B

2011-01-31

Dengue virus infection is a public health threat to hundreds of millions of individuals in the tropical regions of the globe. Although Dengue infection usually manifests itself in its mildest, though often debilitating clinical form, dengue fever, life-threatening complications commonly arise in the form of hemorrhagic shock and encephalitis. The etiological basis for the virus-induced pathology in general, and the different clinical manifestations in particular, are not well understood. We reasoned that a detailed knowledge of the global biological processes affected by virus entry into a cell might help shed new light on this long-standing problem. A bacterial two-hybrid screen using DENV2 structural proteins as bait was performed, and the results were used to feed a manually curated, global dengue-human protein interaction network. Gene ontology and pathway enrichment, along with network topology and microarray meta-analysis, were used to generate hypothesis regarding dengue disease biology. Combining bioinformatic tools with two-hybrid technology, we screened human cDNA libraries to catalogue proteins physically interacting with the DENV2 virus structural proteins, Env, cap and PrM. We identified 31 interacting human proteins representing distinct biological processes that are closely related to the major clinical diagnostic feature of dengue infection: haemostatic imbalance. In addition, we found dengue-binding human proteins involved with additional key aspects, previously described as fundamental for virus entry into cells and the innate immune response to infection. Construction of a DENV2-human global protein interaction network revealed interesting biological properties suggested by simple network topology analysis. Our experimental strategy revealed that dengue structural proteins interact with human protein targets involved in the maintenance of blood coagulation and innate anti-viral response processes, and predicts that the interaction of dengue proteins with a proposed human protein interaction network produces a modified biological outcome that may be behind the hallmark pathologies of dengue infection.

Stability and generalization in seed dispersal networks: a case study of frugivorous fish in Neotropical wetlands.

PubMed

Correa, Sandra Bibiana; Arujo, Joisiane K; Penha, Jerry; Nunes da Cunha, Catia; Bobier, Karen E; Anderson, Jill T

2016-08-31

When species within guilds perform similar ecological roles, functional redundancy can buffer ecosystems against species loss. Using data on the frequency of interactions between fish and fruit, we assessed whether co-occurring frugivores provide redundant seed dispersal services in three species-rich Neotropical wetlands. Our study revealed that frugivorous fishes have generalized diets; however, large-bodied fishes had greater seed dispersal breadth than small species, in some cases, providing seed dispersal services not achieved by smaller fish species. As overfishing disproportionately affects big fishes, the extirpation of these species could cause larger secondary extinctions of plant species than the loss of small specialist frugivores. To evaluate the consequences of frugivore specialization for network stability, we extracted data from 39 published seed dispersal networks of frugivorous birds, mammals and fish (our networks) across ecosystems. Our analysis of interaction frequencies revealed low frugivore specialization and lower nestedness than analyses based on binary data (presence-absence of interactions). In that case, ecosystems may be resilient to loss of any given frugivore. However, robustness to frugivore extinction declines with specialization, such that networks composed primarily of specialist frugivores are highly susceptible to the loss of generalists. In contrast with analyses of binary data, recently developed algorithms capable of modelling interaction strengths provide opportunities to enhance our understanding of complex ecological networks by accounting for heterogeneity of frugivore-fruit interactions. © 2016 The Author(s).

Stability and generalization in seed dispersal networks: a case study of frugivorous fish in Neotropical wetlands

PubMed Central

Arujo, Joisiane K.; Penha, Jerry; Nunes da Cunha, Catia

2016-01-01

When species within guilds perform similar ecological roles, functional redundancy can buffer ecosystems against species loss. Using data on the frequency of interactions between fish and fruit, we assessed whether co-occurring frugivores provide redundant seed dispersal services in three species-rich Neotropical wetlands. Our study revealed that frugivorous fishes have generalized diets; however, large-bodied fishes had greater seed dispersal breadth than small species, in some cases, providing seed dispersal services not achieved by smaller fish species. As overfishing disproportionately affects big fishes, the extirpation of these species could cause larger secondary extinctions of plant species than the loss of small specialist frugivores. To evaluate the consequences of frugivore specialization for network stability, we extracted data from 39 published seed dispersal networks of frugivorous birds, mammals and fish (our networks) across ecosystems. Our analysis of interaction frequencies revealed low frugivore specialization and lower nestedness than analyses based on binary data (presence–absence of interactions). In that case, ecosystems may be resilient to loss of any given frugivore. However, robustness to frugivore extinction declines with specialization, such that networks composed primarily of specialist frugivores are highly susceptible to the loss of generalists. In contrast with analyses of binary data, recently developed algorithms capable of modelling interaction strengths provide opportunities to enhance our understanding of complex ecological networks by accounting for heterogeneity of frugivore–fruit interactions. PMID:27581879

The autophagy interaction network of the aging model Podospora anserina.

PubMed

Philipp, Oliver; Hamann, Andrea; Osiewacz, Heinz D; Koch, Ina

2017-03-27

Autophagy is a conserved molecular pathway involved in the degradation and recycling of cellular components. It is active either as response to starvation or molecular damage. Evidence is emerging that autophagy plays a key role in the degradation of damaged cellular components and thereby affects aging and lifespan control. In earlier studies, it was found that autophagy in the aging model Podospora anserina acts as a longevity assurance mechanism. However, only little is known about the individual components controlling autophagy in this aging model. Here, we report a biochemical and bioinformatics study to detect the protein-protein interaction (PPI) network of P. anserina combining experimental and theoretical methods. We constructed the PPI network of autophagy in P. anserina based on the corresponding networks of yeast and human. We integrated PaATG8 interaction partners identified in an own yeast two-hybrid analysis using ATG8 of P. anserina as bait. Additionally, we included age-dependent transcriptome data. The resulting network consists of 89 proteins involved in 186 interactions. We applied bioinformatics approaches to analyze the network topology and to prove that the network is not random, but exhibits biologically meaningful properties. We identified hub proteins which play an essential role in the network as well as seven putative sub-pathways, and interactions which are likely to be evolutionary conserved amongst species. We confirmed that autophagy-associated genes are significantly often up-regulated and co-expressed during aging of P. anserina. With the present study, we provide a comprehensive biological network of the autophagy pathway in P. anserina comprising PPI and gene expression data. It is based on computational prediction as well as experimental data. We identified sub-pathways, important hub proteins, and evolutionary conserved interactions. The network clearly illustrates the relation of autophagy to aging processes and enables further specific studies to understand autophagy and aging in P. anserina as well as in other systems.

Information jet: Handling noisy big data from weakly disconnected network

NASA Astrophysics Data System (ADS)

Aurongzeb, Deeder

Sudden aggregation (information jet) of large amount of data is ubiquitous around connected social networks, driven by sudden interacting and non-interacting events, network security threat attacks, online sales channel etc. Clustering of information jet based on time series analysis and graph theory is not new but little work is done to connect them with particle jet statistics. We show pre-clustering based on context can element soft network or network of information which is critical to minimize time to calculate results from noisy big data. We show difference between, stochastic gradient boosting and time series-graph clustering. For disconnected higher dimensional information jet, we use Kallenberg representation theorem (Kallenberg, 2005, arXiv:1401.1137) to identify and eliminate jet similarities from dense or sparse graph.

The Influence of Social Network Characteristics on Peer Clustering in Smoking: A Two-Wave Panel Study of 19- and 23-Year-Old Swedes.

PubMed

Miething, Alexander; Rostila, Mikael; Edling, Christofer; Rydgren, Jens

2016-01-01

The present study examines how the composition of social networks and perceived relationship content influence peer clustering in smoking, and how the association changes during the transition from late adolescence to early adulthood. The analysis was based on a Swedish two-wave survey sample comprising ego-centric network data. Respondents were 19 years old in the initial wave, and 23 when the follow-up sample was conducted. 17,227 ego-alter dyads were included in the analyses, which corresponds to an average response rate of 48.7 percent. Random effects logistic regression models were performed to calculate gender-specific average marginal effects of social network characteristics on smoking. The association of egos' and alters' smoking behavior was confirmed and found to be stronger when correlated in the female sample. For females, the associations decreased between age 19 and 23. Interactions between network characteristics and peer clustering in smoking showed that intense social interactions with smokers increase egos' smoking probability. The influence of network structures on peer clustering in smoking decreased during the transition from late adolescence to early adulthood. The study confirmed peer clustering in smoking and revealed that females' smoking behavior in particular is determined by social interactions. Female smokers' propensity to interact with other smokers was found to be associated with the quality of peer relationships, frequent social interactions, and network density. The influence of social networks on peer clustering in smoking decreased during the transition from late adolescence to early adulthood.

The Influence of Social Network Characteristics on Peer Clustering in Smoking: A Two-Wave Panel Study of 19- and 23-Year-Old Swedes

PubMed Central

Rostila, Mikael; Edling, Christofer; Rydgren, Jens

2016-01-01

Objectives The present study examines how the composition of social networks and perceived relationship content influence peer clustering in smoking, and how the association changes during the transition from late adolescence to early adulthood. Methods The analysis was based on a Swedish two-wave survey sample comprising ego-centric network data. Respondents were 19 years old in the initial wave, and 23 when the follow-up sample was conducted. 17,227 ego-alter dyads were included in the analyses, which corresponds to an average response rate of 48.7 percent. Random effects logistic regression models were performed to calculate gender-specific average marginal effects of social network characteristics on smoking. Results The association of egos’ and alters’ smoking behavior was confirmed and found to be stronger when correlated in the female sample. For females, the associations decreased between age 19 and 23. Interactions between network characteristics and peer clustering in smoking showed that intense social interactions with smokers increase egos’ smoking probability. The influence of network structures on peer clustering in smoking decreased during the transition from late adolescence to early adulthood. Conclusions The study confirmed peer clustering in smoking and revealed that females’ smoking behavior in particular is determined by social interactions. Female smokers’ propensity to interact with other smokers was found to be associated with the quality of peer relationships, frequent social interactions, and network density. The influence of social networks on peer clustering in smoking decreased during the transition from late adolescence to early adulthood. PMID:27727314

A high-resolution human contact network for infectious disease transmission

PubMed Central

Salathé, Marcel; Kazandjieva, Maria; Lee, Jung Woo; Levis, Philip; Feldman, Marcus W.; Jones, James H.

2010-01-01

The most frequent infectious diseases in humans—and those with the highest potential for rapid pandemic spread—are usually transmitted via droplets during close proximity interactions (CPIs). Despite the importance of this transmission route, very little is known about the dynamic patterns of CPIs. Using wireless sensor network technology, we obtained high-resolution data of CPIs during a typical day at an American high school, permitting the reconstruction of the social network relevant for infectious disease transmission. At 94% coverage, we collected 762,868 CPIs at a maximal distance of 3 m among 788 individuals. The data revealed a high-density network with typical small-world properties and a relatively homogeneous distribution of both interaction time and interaction partners among subjects. Computer simulations of the spread of an influenza-like disease on the weighted contact graph are in good agreement with absentee data during the most recent influenza season. Analysis of targeted immunization strategies suggested that contact network data are required to design strategies that are significantly more effective than random immunization. Immunization strategies based on contact network data were most effective at high vaccination coverage. PMID:21149721

Estimates of segregation and overlap of functional connectivity networks in the human cerebral cortex.

PubMed

Yeo, B T Thomas; Krienen, Fenna M; Chee, Michael W L; Buckner, Randy L

2014-03-01

The organization of the human cerebral cortex has recently been explored using techniques for parcellating the cortex into distinct functionally coupled networks. The divergent and convergent nature of cortico-cortical anatomic connections suggests the need to consider the possibility of regions belonging to multiple networks and hierarchies among networks. Here we applied the Latent Dirichlet Allocation (LDA) model and spatial independent component analysis (ICA) to solve for functionally coupled cerebral networks without assuming that cortical regions belong to a single network. Data analyzed included 1000 subjects from the Brain Genomics Superstruct Project (GSP) and 12 high quality individual subjects from the Human Connectome Project (HCP). The organization of the cerebral cortex was similar regardless of whether a winner-take-all approach or the more relaxed constraints of LDA (or ICA) were imposed. This suggests that large-scale networks may function as partially isolated modules. Several notable interactions among networks were uncovered by the LDA analysis. Many association regions belong to at least two networks, while somatomotor and early visual cortices are especially isolated. As examples of interaction, the precuneus, lateral temporal cortex, medial prefrontal cortex and posterior parietal cortex participate in multiple paralimbic networks that together comprise subsystems of the default network. In addition, regions at or near the frontal eye field and human lateral intraparietal area homologue participate in multiple hierarchically organized networks. These observations were replicated in both datasets and could be detected (and replicated) in individual subjects from the HCP. © 2013.

Estimates of Segregation and Overlap of Functional Connectivity Networks in the Human Cerebral Cortex

PubMed Central

Yeo, BT Thomas; Krienen, Fenna M; Chee, Michael WL; Buckner, Randy L

2014-01-01

The organization of the human cerebral cortex has recently been explored using techniques for parcellating the cortex into distinct functionally coupled networks. The divergent and convergent nature of cortico-cortical anatomic connections suggests the need to consider the possibility of regions belonging to multiple networks and hierarchies among networks. Here we applied the Latent Dirichlet Allocation (LDA) model and spatial independent component analysis (ICA) to solve for functionally coupled cerebral networks without assuming that cortical regions belong to a single network. Data analyzed included 1,000 subjects from the Brain Genomics Superstruct Project (GSP) and 12 high quality individual subjects from the Human Connectome Project (HCP). The organization of the cerebral cortex was similar regardless of whether a winner-take-all approach or the more relaxed constraints of LDA (or ICA) were imposed. This suggests that large-scale networks may function as partially isolated modules. Several notable interactions among networks were uncovered by the LDA analysis. Many association regions belong to at least two networks, while somatomotor and early visual cortices are especially isolated. As examples of interaction, the precuneus, lateral temporal cortex, medial prefrontal cortex and posterior parietal cortex participate in multiple paralimbic networks that together comprise subsystems of the default network. In addition, regions at or near the frontal eye field and human lateral intraparietal area homologue participate in multiple hierarchically organized networks. These observations were replicated in both datasets and could be detected (and replicated) in individual subjects from the HCP. PMID:24185018

Innovation diffusion on time-varying activity driven networks

NASA Astrophysics Data System (ADS)

Rizzo, Alessandro; Porfiri, Maurizio

2016-01-01

Since its introduction in the 1960s, the theory of innovation diffusion has contributed to the advancement of several research fields, such as marketing management and consumer behavior. The 1969 seminal paper by Bass [F.M. Bass, Manag. Sci. 15, 215 (1969)] introduced a model of product growth for consumer durables, which has been extensively used to predict innovation diffusion across a range of applications. Here, we propose a novel approach to study innovation diffusion, where interactions among individuals are mediated by the dynamics of a time-varying network. Our approach is based on the Bass' model, and overcomes key limitations of previous studies, which assumed timescale separation between the individual dynamics and the evolution of the connectivity patterns. Thus, we do not hypothesize homogeneous mixing among individuals or the existence of a fixed interaction network. We formulate our approach in the framework of activity driven networks to enable the analysis of the concurrent evolution of the interaction and individual dynamics. Numerical simulations offer a systematic analysis of the model behavior and highlight the role of individual activity on market penetration when targeted advertisement campaigns are designed, or a competition between two different products takes place.

Pathway Interaction Network Analysis Identifies Dysregulated Pathways in Human Monocytes Infected by Listeria monocytogenes.

PubMed

Fan, Wufeng; Zhou, Yuhan; Li, Hao

2017-01-01

In our study, we aimed to extract dysregulated pathways in human monocytes infected by Listeria monocytogenes (LM) based on pathway interaction network (PIN) which presented the functional dependency between pathways. After genes were aligned to the pathways, principal component analysis (PCA) was used to calculate the pathway activity for each pathway, followed by detecting seed pathway. A PIN was constructed based on gene expression profile, protein-protein interactions (PPIs), and cellular pathways. Identifying dysregulated pathways from the PIN was performed relying on seed pathway and classification accuracy. To evaluate whether the PIN method was feasible or not, we compared the introduced method with standard network centrality measures. The pathway of RNA polymerase II pretranscription events was selected as the seed pathway. Taking this seed pathway as start, one pathway set (9 dysregulated pathways) with AUC score of 1.00 was identified. Among the 5 hub pathways obtained using standard network centrality measures, 4 pathways were the common ones between the two methods. RNA polymerase II transcription and DNA replication owned a higher number of pathway genes and DEGs. These dysregulated pathways work together to influence the progression of LM infection, and they will be available as biomarkers to diagnose LM infection.

Functional Connectivity of Child and Adolescent Attention Deficit Hyperactivity Disorder Patients: Correlation with IQ.

PubMed

Park, Bo-Yong; Hong, Jisu; Lee, Seung-Hak; Park, Hyunjin

2016-01-01

Attention deficit hyperactivity disorder (ADHD) is a pervasive neuropsychological disorder that affects both children and adolescents. Child and adolescent ADHD patients exhibit different behavioral symptoms such as hyperactivity and impulsivity, but not much connectivity research exists to help explain these differences. We analyzed openly accessible resting-state functional magnetic resonance imaging (rs-fMRI) data on 112 patients (28 child ADHD, 28 adolescent ADHD, 28 child normal control (NC), and 28 adolescent NC). We used group independent component analysis (ICA) and weighted degree values to identify interaction effects of age (child and adolescent) and symptom (ADHD and NC) in brain networks. The frontoparietal network showed significant interaction effects ( p = 0.0068). The frontoparietal network is known to be related to hyperactive and impulsive behaviors. Intelligence quotient (IQ) is an important factor in ADHD, and we predicted IQ scores using the results of our connectivity analysis. IQ was predicted using degree centrality values of networks with significant interaction effects of age and symptom. Actual and predicted IQ scores demonstrated significant correlation values, with an error of about 10%. Our study might provide imaging biomarkers for future ADHD and intelligence studies.

FUSE: a profit maximization approach for functional summarization of biological networks.

PubMed

Seah, Boon-Siew; Bhowmick, Sourav S; Dewey, C Forbes; Yu, Hanry

2012-03-21

The availability of large-scale curated protein interaction datasets has given rise to the opportunity to investigate higher level organization and modularity within the protein interaction network (PPI) using graph theoretic analysis. Despite the recent progress, systems level analysis of PPIS remains a daunting task as it is challenging to make sense out of the deluge of high-dimensional interaction data. Specifically, techniques that automatically abstract and summarize PPIS at multiple resolutions to provide high level views of its functional landscape are still lacking. We present a novel data-driven and generic algorithm called FUSE (Functional Summary Generator) that generates functional maps of a PPI at different levels of organization, from broad process-process level interactions to in-depth complex-complex level interactions, through a pro t maximization approach that exploits Minimum Description Length (MDL) principle to maximize information gain of the summary graph while satisfying the level of detail constraint. We evaluate the performance of FUSE on several real-world PPIS. We also compare FUSE to state-of-the-art graph clustering methods with GO term enrichment by constructing the biological process landscape of the PPIS. Using AD network as our case study, we further demonstrate the ability of FUSE to quickly summarize the network and identify many different processes and complexes that regulate it. Finally, we study the higher-order connectivity of the human PPI. By simultaneously evaluating interaction and annotation data, FUSE abstracts higher-order interaction maps by reducing the details of the underlying PPI to form a functional summary graph of interconnected functional clusters. Our results demonstrate its effectiveness and superiority over state-of-the-art graph clustering methods with GO term enrichment.

CI-KNOW: Cyberinfrastructure Knowledge Networks on the Web. A Social Network Enabled Recommender System for Locating Resources in Cyberinfrastructures

NASA Astrophysics Data System (ADS)

Green, H. D.; Contractor, N. S.; Yao, Y.

2006-12-01

A knowledge network is a multi-dimensional network created from the interactions and interconnections among the scientists, documents, data, analytic tools, and interactive collaboration spaces (like forums and wikis) associated with a collaborative environment. CI-KNOW is a suite of software tools that leverages automated data collection, social network theories, analysis techniques and algorithms to infer an individual's interests and expertise based on their interactions and activities within a knowledge network. The CI-KNOW recommender system mines the knowledge network associated with a scientific community's use of cyberinfrastructure tools and uses relational metadata to record connections among entities in the knowledge network. Recent developments in social network theories and methods provide the backbone for a modular system that creates recommendations from relational metadata. A network navigation portlet allows users to locate colleagues, documents, data or analytic tools in the knowledge network and to explore their networks through a visual, step-wise process. An internal auditing portlet offers administrators diagnostics to assess the growth and health of the entire knowledge network. The first instantiation of the prototype CI-KNOW system is part of the Environmental Cyberinfrastructure Demonstration project at the National Center for Supercomputing Applications, which supports the activities of hydrologic and environmental science communities (CLEANER and CUAHSI) under the umbrella of the WATERS network environmental observatory planning activities (http://cleaner.ncsa.uiuc.edu). This poster summarizes the key aspects of the CI-KNOW system, highlighting the key inputs, calculation mechanisms, and output modalities.

Functional Module Search in Protein Networks based on Semantic Similarity Improves the Analysis of Proteomics Data*

PubMed Central

Boyanova, Desislava; Nilla, Santosh; Klau, Gunnar W.; Dandekar, Thomas; Müller, Tobias; Dittrich, Marcus

2014-01-01

The continuously evolving field of proteomics produces increasing amounts of data while improving the quality of protein identifications. Albeit quantitative measurements are becoming more popular, many proteomic studies are still based on non-quantitative methods for protein identification. These studies result in potentially large sets of identified proteins, where the biological interpretation of proteins can be challenging. Systems biology develops innovative network-based methods, which allow an integrated analysis of these data. Here we present a novel approach, which combines prior knowledge of protein-protein interactions (PPI) with proteomics data using functional similarity measurements of interacting proteins. This integrated network analysis exactly identifies network modules with a maximal consistent functional similarity reflecting biological processes of the investigated cells. We validated our approach on small (H9N2 virus-infected gastric cells) and large (blood constituents) proteomic data sets. Using this novel algorithm, we identified characteristic functional modules in virus-infected cells, comprising key signaling proteins (e.g. the stress-related kinase RAF1) and demonstrate that this method allows a module-based functional characterization of cell types. Analysis of a large proteome data set of blood constituents resulted in clear separation of blood cells according to their developmental origin. A detailed investigation of the T-cell proteome further illustrates how the algorithm partitions large networks into functional subnetworks each representing specific cellular functions. These results demonstrate that the integrated network approach not only allows a detailed analysis of proteome networks but also yields a functional decomposition of complex proteomic data sets and thereby provides deeper insights into the underlying cellular processes of the investigated system. PMID:24807868

Characterizing interactions in online social networks during exceptional events

NASA Astrophysics Data System (ADS)

Omodei, Elisa; De Domenico, Manlio; Arenas, Alex

2015-08-01

Nowadays, millions of people interact on a daily basis on online social media like Facebook and Twitter, where they share and discuss information about a wide variety of topics. In this paper, we focus on a specific online social network, Twitter, and we analyze multiple datasets each one consisting of individuals' online activity before, during and after an exceptional event in terms of volume of the communications registered. We consider important events that occurred in different arenas that range from policy to culture or science. For each dataset, the users' online activities are modeled by a multilayer network in which each layer conveys a different kind of interaction, specifically: retweeting, mentioning and replying. This representation allows us to unveil that these distinct types of interaction produce networks with different statistical properties, in particular concerning the degree distribution and the clustering structure. These results suggests that models of online activity cannot discard the information carried by this multilayer representation of the system, and should account for the different processes generated by the different kinds of interactions. Secondly, our analysis unveils the presence of statistical regularities among the different events, suggesting that the non-trivial topological patterns that we observe may represent universal features of the social dynamics on online social networks during exceptional events.

fabp4 is central to eight obesity associated genes: a functional gene network-based polymorphic study.

PubMed

Bag, Susmita; Ramaiah, Sudha; Anbarasu, Anand

2015-01-07

Network study on genes and proteins offers functional basics of the complexity of gene and protein, and its interacting partners. The gene fatty acid-binding protein 4 (fabp4) is found to be highly expressed in adipose tissue, and is one of the most abundant proteins in mature adipocytes. Our investigations on functional modules of fabp4 provide useful information on the functional genes interacting with fabp4, their biochemical properties and their regulatory functions. The present study shows that there are eight set of candidate genes: acp1, ext2, insr, lipe, ostf1, sncg, usp15, and vim that are strongly and functionally linked up with fabp4. Gene ontological analysis of network modules of fabp4 provides an explicit idea on the functional aspect of fabp4 and its interacting nodes. The hierarchal mapping on gene ontology indicates gene specific processes and functions as well as their compartmentalization in tissues. The fabp4 along with its interacting genes are involved in lipid metabolic activity and are integrated in multi-cellular processes of tissues and organs. They also have important protein/enzyme binding activity. Our study elucidated disease-associated nsSNP prediction for fabp4 and it is interesting to note that there are four rsID׳s (rs1051231, rs3204631, rs140925685 and rs141169989) with disease allelic variation (T104P, T126P, G27D and G90V respectively). On the whole, our gene network analysis presents a clear insight about the interactions and functions associated with fabp4 gene network. Copyright © 2014 Elsevier Ltd. All rights reserved.

Algorithm to Identify Frequent Coupled Modules from Two-Layered Network Series: Application to Study Transcription and Splicing Coupling

PubMed Central

Li, Wenyuan; Dai, Chao; Liu, Chun-Chi

2012-01-01

Abstract Current network analysis methods all focus on one or multiple networks of the same type. However, cells are organized by multi-layer networks (e.g., transcriptional regulatory networks, splicing regulatory networks, protein-protein interaction networks), which interact and influence each other. Elucidating the coupling mechanisms among those different types of networks is essential in understanding the functions and mechanisms of cellular activities. In this article, we developed the first computational method for pattern mining across many two-layered graphs, with the two layers representing different types yet coupled biological networks. We formulated the problem of identifying frequent coupled clusters between the two layers of networks into a tensor-based computation problem, and proposed an efficient solution to solve the problem. We applied the method to 38 two-layered co-transcription and co-splicing networks, derived from 38 RNA-seq datasets. With the identified atlas of coupled transcription-splicing modules, we explored to what extent, for which cellular functions, and by what mechanisms transcription-splicing coupling takes place. PMID:22697243

Rhizoma Dioscoreae extract protects against alveolar bone loss by regulating the cell cycle: A predictive study based on the protein‑protein interaction network.

PubMed

Zhang, Zhi-Guo; Song, Chang-Heng; Zhang, Fang-Zhen; Chen, Yan-Jing; Xiang, Li-Hua; Xiao, Gary Guishan; Ju, Da-Hong

2016-06-01

Rhizoma Dioscoreae extract (RDE) exhibits a protective effect on alveolar bone loss in ovariectomized (OVX) rats. The aim of this study was to predict the pathways or targets that are regulated by RDE, by re‑assessing our previously reported data and conducting a protein‑protein interaction (PPI) network analysis. In total, 383 differentially expressed genes (≥3‑fold) between alveolar bone samples from the RDE and OVX group rats were identified, and a PPI network was constructed based on these genes. Furthermore, four molecular clusters (A‑D) in the PPI network with the smallest P‑values were detected by molecular complex detection (MCODE) algorithm. Using Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity Pathway Analysis (IPA) tools, two molecular clusters (A and B) were enriched for biological process in Gene Ontology (GO). Only cluster A was associated with biological pathways in the IPA database. GO and pathway analysis results showed that cluster A, associated with cell cycle regulation, was the most important molecular cluster in the PPI network. In addition, cyclin‑dependent kinase 1 (CDK1) may be a key molecule achieving the cell‑cycle‑regulatory function of cluster A. From the PPI network analysis, it was predicted that delayed cell cycle progression in excessive alveolar bone remodeling via downregulation of CDK1 may be another mechanism underling the anti‑osteopenic effect of RDE on alveolar bone.

FoodMicrobionet: A database for the visualisation and exploration of food bacterial communities based on network analysis.

PubMed

Parente, Eugenio; Cocolin, Luca; De Filippis, Francesca; Zotta, Teresa; Ferrocino, Ilario; O'Sullivan, Orla; Neviani, Erasmo; De Angelis, Maria; Cotter, Paul D; Ercolini, Danilo

2016-02-16

Amplicon targeted high-throughput sequencing has become a popular tool for the culture-independent analysis of microbial communities. Although the data obtained with this approach are portable and the number of sequences available in public databases is increasing, no tool has been developed yet for the analysis and presentation of data obtained in different studies. This work describes an approach for the development of a database for the rapid exploration and analysis of data on food microbial communities. Data from seventeen studies investigating the structure of bacterial communities in dairy, meat, sourdough and fermented vegetable products, obtained by 16S rRNA gene targeted high-throughput sequencing, were collated and analysed using Gephi, a network analysis software. The resulting database, which we named FoodMicrobionet, was used to analyse nodes and network properties and to build an interactive web-based visualisation. The latter allows the visual exploration of the relationships between Operational Taxonomic Units (OTUs) and samples and the identification of core- and sample-specific bacterial communities. It also provides additional search tools and hyperlinks for the rapid selection of food groups and OTUs and for rapid access to external resources (NCBI taxonomy, digital versions of the original articles). Microbial interaction network analysis was carried out using CoNet on datasets extracted from FoodMicrobionet: the complexity of interaction networks was much lower than that found for other bacterial communities (human microbiome, soil and other environments). This may reflect both a bias in the dataset (which was dominated by fermented foods and starter cultures) and the lower complexity of food bacterial communities. Although some technical challenges exist, and are discussed here, the net result is a valuable tool for the exploration of food bacterial communities by the scientific community and food industry. Copyright © 2015. Published by Elsevier B.V.

XLinkDB 2.0: integrated, large-scale structural analysis of protein crosslinking data

PubMed Central

Schweppe, Devin K.; Zheng, Chunxiang; Chavez, Juan D.; Navare, Arti T.; Wu, Xia; Eng, Jimmy K.; Bruce, James E.

2016-01-01

Motivation: Large-scale chemical cross-linking with mass spectrometry (XL-MS) analyses are quickly becoming a powerful means for high-throughput determination of protein structural information and protein–protein interactions. Recent studies have garnered thousands of cross-linked interactions, yet the field lacks an effective tool to compile experimental data or access the network and structural knowledge for these large scale analyses. We present XLinkDB 2.0 which integrates tools for network analysis, Protein Databank queries, modeling of predicted protein structures and modeling of docked protein structures. The novel, integrated approach of XLinkDB 2.0 enables the holistic analysis of XL-MS protein interaction data without limitation to the cross-linker or analytical system used for the analysis. Availability and Implementation: XLinkDB 2.0 can be found here, including documentation and help: http://xlinkdb.gs.washington.edu/. Contact: jimbruce@uw.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27153666

Inferring protein domains associated with drug side effects based on drug-target interaction network.

PubMed

Iwata, Hiroaki; Mizutani, Sayaka; Tabei, Yasuo; Kotera, Masaaki; Goto, Susumu; Yamanishi, Yoshihiro

2013-01-01

Most phenotypic effects of drugs are involved in the interactions between drugs and their target proteins, however, our knowledge about the molecular mechanism of the drug-target interactions is very limited. One of challenging issues in recent pharmaceutical science is to identify the underlying molecular features which govern drug-target interactions. In this paper, we make a systematic analysis of the correlation between drug side effects and protein domains, which we call "pharmacogenomic features," based on the drug-target interaction network. We detect drug side effects and protein domains that appear jointly in known drug-target interactions, which is made possible by using classifiers with sparse models. It is shown that the inferred pharmacogenomic features can be used for predicting potential drug-target interactions. We also discuss advantages and limitations of the pharmacogenomic features, compared with the chemogenomic features that are the associations between drug chemical substructures and protein domains. The inferred side effect-domain association network is expected to be useful for estimating common drug side effects for different protein families and characteristic drug side effects for specific protein domains.

Visualization of protein interaction networks: problems and solutions

PubMed Central

2013-01-01

Background Visualization concerns the representation of data visually and is an important task in scientific research. Protein-protein interactions (PPI) are discovered using either wet lab techniques, such mass spectrometry, or in silico predictions tools, resulting in large collections of interactions stored in specialized databases. The set of all interactions of an organism forms a protein-protein interaction network (PIN) and is an important tool for studying the behaviour of the cell machinery. Since graphic representation of PINs may highlight important substructures, e.g. protein complexes, visualization is more and more used to study the underlying graph structure of PINs. Although graphs are well known data structures, there are different open problems regarding PINs visualization: the high number of nodes and connections, the heterogeneity of nodes (proteins) and edges (interactions), the possibility to annotate proteins and interactions with biological information extracted by ontologies (e.g. Gene Ontology) that enriches the PINs with semantic information, but complicates their visualization. Methods In these last years many software tools for the visualization of PINs have been developed. Initially thought for visualization only, some of them have been successively enriched with new functions for PPI data management and PIN analysis. The paper analyzes the main software tools for PINs visualization considering four main criteria: (i) technology, i.e. availability/license of the software and supported OS (Operating System) platforms; (ii) interoperability, i.e. ability to import/export networks in various formats, ability to export data in a graphic format, extensibility of the system, e.g. through plug-ins; (iii) visualization, i.e. supported layout and rendering algorithms and availability of parallel implementation; (iv) analysis, i.e. availability of network analysis functions, such as clustering or mining of the graph, and the possibility to interact with external databases. Results Currently, many tools are available and it is not easy for the users choosing one of them. Some tools offer sophisticated 2D and 3D network visualization making available many layout algorithms, others tools are more data-oriented and support integration of interaction data coming from different sources and data annotation. Finally, some specialistic tools are dedicated to the analysis of pathways and cellular processes and are oriented toward systems biology studies, where the dynamic aspects of the processes being studied are central. Conclusion A current trend is the deployment of open, extensible visualization tools (e.g. Cytoscape), that may be incrementally enriched by the interactomics community with novel and more powerful functions for PIN analysis, through the development of plug-ins. On the other hand, another emerging trend regards the efficient and parallel implementation of the visualization engine that may provide high interactivity and near real-time response time, as in NAViGaTOR. From a technological point of view, open-source, free and extensible tools, like Cytoscape, guarantee a long term sustainability due to the largeness of the developers and users communities, and provide a great flexibility since new functions are continuously added by the developer community through new plug-ins, but the emerging parallel, often closed-source tools like NAViGaTOR, can offer near real-time response time also in the analysis of very huge PINs. PMID:23368786

Pattern Formation on Networks: from Localised Activity to Turing Patterns

PubMed Central

McCullen, Nick; Wagenknecht, Thomas

2016-01-01

Networks of interactions between competing species are used to model many complex systems, such as in genetics, evolutionary biology or sociology and knowledge of the patterns of activity they can exhibit is important for understanding their behaviour. The emergence of patterns on complex networks with reaction-diffusion dynamics is studied here, where node dynamics interact via diffusion via the network edges. Through the application of a generalisation of dynamical systems analysis this work reveals a fundamental connection between small-scale modes of activity on networks and localised pattern formation seen throughout science, such as solitons, breathers and localised buckling. The connection between solutions with a single and small numbers of activated nodes and the fully developed system-scale patterns are investigated computationally using numerical continuation methods. These techniques are also used to help reveal a much larger portion of of the full number of solutions that exist in the system at different parameter values. The importance of network structure is also highlighted, with a key role being played by nodes with a certain so-called optimal degree, on which the interaction between the reaction kinetics and the network structure organise the behaviour of the system. PMID:27273339

Revealing the potential pathogenesis of glioma by utilizing a glioma associated protein-protein interaction network.

PubMed

Pan, Weiran; Li, Gang; Yang, Xiaoxiao; Miao, Jinming

2015-04-01

This study aims to explore the potential mechanism of glioma through bioinformatic approaches. The gene expression profile (GSE4290) of glioma tumor and non-tumor samples was downloaded from Gene Expression Omnibus database. A total of 180 samples were available, including 23 non-tumor and 157 tumor samples. Then the raw data were preprocessed using robust multiarray analysis, and 8,890 differentially expressed genes (DEGs) were identified by using t-test (false discovery rate < 0.0005). Furthermore, 16 known glioma related genes were abstracted from Genetic Association Database. After mapping 8,890 DEGs and 16 known glioma related genes to Human Protein Reference Database, a glioma associated protein-protein interaction network (GAPN) was constructed. In addition, 51 sub-networks in GAPN were screened out through Molecular Complex Detection (score ≥ 1), and sub-network 1 was found to have the closest interaction (score = 3). What' more, for the top 10 sub-networks, Gene Ontology (GO) enrichment analysis (p value < 0.05) was performed, and DEGs involved in sub-network 1 and 2, such as BRMS1L and CCNA1, were predicted to regulate cell growth, cell cycle, and DNA replication via interacting with known glioma related genes. Finally, the overlaps of DEGs and human essential, housekeeping, tissue-specific genes were calculated (p value = 1.0, 1.0, and 0.00014, respectively) and visualized by Venn Diagram package in R. About 61% of human tissue-specific genes were DEGs as well. This research shed new light on the pathogenesis of glioma based on DEGs and GAPN, and our findings might provide potential targets for clinical glioma treatment.

Using the relational event model (REM) to investigate the temporal dynamics of animal social networks.

PubMed

Tranmer, Mark; Marcum, Christopher Steven; Morton, F Blake; Croft, Darren P; de Kort, Selvino R

2015-03-01

Social dynamics are of fundamental importance in animal societies. Studies on nonhuman animal social systems often aggregate social interaction event data into a single network within a particular time frame. Analysis of the resulting network can provide a useful insight into the overall extent of interaction. However, through aggregation, information is lost about the order in which interactions occurred, and hence the sequences of actions over time. Many research hypotheses relate directly to the sequence of actions, such as the recency or rate of action, rather than to their overall volume or presence. Here, we demonstrate how the temporal structure of social interaction sequences can be quantified from disaggregated event data using the relational event model (REM). We first outline the REM, explaining why it is different from other models for longitudinal data, and how it can be used to model sequences of events unfolding in a network. We then discuss a case study on the European jackdaw, Corvus monedula , in which temporal patterns of persistence and reciprocity of action are of interest, and present and discuss the results of a REM analysis of these data. One of the strengths of a REM analysis is its ability to take into account different ways in which data are collected. Having explained how to take into account the way in which the data were collected for the jackdaw study, we briefly discuss the application of the model to other studies. We provide details of how the models may be fitted in the R statistical software environment and outline some recent extensions to the REM framework.

Complementary molecular information changes our perception of food web structure

PubMed Central

Wirta, Helena K.; Hebert, Paul D. N.; Kaartinen, Riikka; Prosser, Sean W.; Várkonyi, Gergely; Roslin, Tomas

2014-01-01

How networks of ecological interactions are structured has a major impact on their functioning. However, accurately resolving both the nodes of the webs and the links between them is fraught with difficulties. We ask whether the new resolution conferred by molecular information changes perceptions of network structure. To probe a network of antagonistic interactions in the High Arctic, we use two complementary sources of molecular data: parasitoid DNA sequenced from the tissues of their hosts and host DNA sequenced from the gut of adult parasitoids. The information added by molecular analysis radically changes the properties of interaction structure. Overall, three times as many interaction types were revealed by combining molecular information from parasitoids and hosts with rearing data, versus rearing data alone. At the species level, our results alter the perceived host specificity of parasitoids, the parasitoid load of host species, and the web-wide role of predators with a cryptic lifestyle. As the northernmost network of host–parasitoid interactions quantified, our data point exerts high leverage on global comparisons of food web structure. However, how we view its structure will depend on what information we use: compared with variation among networks quantified at other sites, the properties of our web vary as much or much more depending on the techniques used to reconstruct it. We thus urge ecologists to combine multiple pieces of evidence in assessing the structure of interaction webs, and suggest that current perceptions of interaction structure may be strongly affected by the methods used to construct them. PMID:24449902

HubAlign: an accurate and efficient method for global alignment of protein-protein interaction networks.

PubMed

Hashemifar, Somaye; Xu, Jinbo

2014-09-01

High-throughput experimental techniques have produced a large amount of protein-protein interaction (PPI) data. The study of PPI networks, such as comparative analysis, shall benefit the understanding of life process and diseases at the molecular level. One way of comparative analysis is to align PPI networks to identify conserved or species-specific subnetwork motifs. A few methods have been developed for global PPI network alignment, but it still remains challenging in terms of both accuracy and efficiency. This paper presents a novel global network alignment algorithm, denoted as HubAlign, that makes use of both network topology and sequence homology information, based upon the observation that topologically important proteins in a PPI network usually are much more conserved and thus, more likely to be aligned. HubAlign uses a minimum-degree heuristic algorithm to estimate the topological and functional importance of a protein from the global network topology information. Then HubAlign aligns topologically important proteins first and gradually extends the alignment to the whole network. Extensive tests indicate that HubAlign greatly outperforms several popular methods in terms of both accuracy and efficiency, especially in detecting functionally similar proteins. HubAlign is available freely for non-commercial purposes at http://ttic.uchicago.edu/∼hashemifar/software/HubAlign.zip. Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press.

A network approach of gene co-expression in the zea mays/Aspergillus flavus pathosystem to map host/pathogen interaction pathways

USDA-ARS?s Scientific Manuscript database

A gene co-expression network was generated using a dual RNA-seq study with the fungal pathogen A. flavus and its plant host Z. mays during the initial 3 days of infection. The analysis deciphered novel pathways and mapped genes of interest in both organisms during the infection. This network reveal...

Dynamical network interactions in distributed control of robots

NASA Astrophysics Data System (ADS)

Buscarino, Arturo; Fortuna, Luigi; Frasca, Mattia; Rizzo, Alessandro

2006-03-01

In this paper the dynamical network model of the interactions within a group of mobile robots is investigated and proposed as a possible strategy for controlling the robots without central coordination. Motivated by the results of the analysis of our simple model, we show that the system performance in the presence of noise can be improved by including long-range connections between the robots. Finally, a suitable strategy based on this model to control exploration and transport is introduced.

Investigation on Law and Economics Based on Complex Network and Time Series Analysis

PubMed Central

Yang, Jian; Qu, Zhao; Chang, Hui

2015-01-01

The research focuses on the cooperative relationship and the strategy tendency among three mutually interactive parties in financing: small enterprises, commercial banks and micro-credit companies. Complex network theory and time series analysis were applied to figure out the quantitative evidence. Moreover, this paper built up a fundamental model describing the particular interaction among them through evolutionary game. Combining the results of data analysis and current situation, it is justifiable to put forward reasonable legislative recommendations for regulations on lending activities among small enterprises, commercial banks and micro-credit companies. The approach in this research provides a framework for constructing mathematical models and applying econometrics and evolutionary game in the issue of corporation financing. PMID:26076460

Affinity purification–mass spectrometry and network analysis to understand protein-protein interactions

PubMed Central

Morris, John H; Knudsen, Giselle M; Verschueren, Erik; Johnson, Jeffrey R; Cimermancic, Peter; Greninger, Alexander L; Pico, Alexander R

2015-01-01

By determining protein-protein interactions in normal, diseased and infected cells, we can improve our understanding of cellular systems and their reaction to various perturbations. In this protocol, we discuss how to use data obtained in affinity purification–mass spectrometry (AP-MS) experiments to generate meaningful interaction networks and effective figures. We begin with an overview of common epitope tagging, expression and AP practices, followed by liquid chromatography–MS (LC-MS) data collection. We then provide a detailed procedure covering a pipeline approach to (i) pre-processing the data by filtering against contaminant lists such as the Contaminant Repository for Affinity Purification (CRAPome) and normalization using the spectral index (SIN) or normalized spectral abundance factor (NSAF); (ii) scoring via methods such as MiST, SAInt and CompPASS; and (iii) testing the resulting scores. Data formats familiar to MS practitioners are then transformed to those most useful for network-based analyses. The protocol also explores methods available in Cytoscape to visualize and analyze these types of interaction data. The scoring pipeline can take anywhere from 1 d to 1 week, depending on one’s familiarity with the tools and data peculiarities. Similarly, the network analysis and visualization protocol in Cytoscape takes 2–4 h to complete with the provided sample data, but we recommend taking days or even weeks to explore one’s data and find the right questions. PMID:25275790

Causal structure of oscillations in gene regulatory networks: Boolean analysis of ordinary differential equation attractors.

PubMed

Sun, Mengyang; Cheng, Xianrui; Socolar, Joshua E S

2013-06-01

A common approach to the modeling of gene regulatory networks is to represent activating or repressing interactions using ordinary differential equations for target gene concentrations that include Hill function dependences on regulator gene concentrations. An alternative formulation represents the same interactions using Boolean logic with time delays associated with each network link. We consider the attractors that emerge from the two types of models in the case of a simple but nontrivial network: a figure-8 network with one positive and one negative feedback loop. We show that the different modeling approaches give rise to the same qualitative set of attractors with the exception of a possible fixed point in the ordinary differential equation model in which concentrations sit at intermediate values. The properties of the attractors are most easily understood from the Boolean perspective, suggesting that time-delay Boolean modeling is a useful tool for understanding the logic of regulatory networks.

An integrative system biology approach to unravel potential drug candidates for multiple age related disorders.

PubMed

Srivastava, Isha; Khurana, Pooja; Yadav, Mohini; Hasija, Yasha

2017-12-01

Aging, though an inevitable part of life, is becoming a worldwide social and economic problem. Healthy aging is usually marked by low probability of age related disorders. Good therapeutic approaches are still in need to cure age related disorders. Occurrence of more than one ARD in an individual, expresses the need of discovery of such target proteins, which can affect multiple ARDs. Advanced scientific and medical research technologies throughout last three decades have arrived to the point where lots of key molecular determinants affect human disorders can be examined thoroughly. In this study, we designed and executed an approach to prioritize drugs that may target multiple age related disorders. Our methodology, focused on the analysis of biological pathways and protein protein interaction networks that may contribute to the pharmacology of age related disorders, included various steps such as retrieval and analysis of data, protein-protein interaction network analysis, and statistical and comparative analysis of topological coefficients, pathway, and functional enrichment analysis, and identification of drug-target proteins. We assume that the identified molecular determinants may be prioritized for further screening as novel drug targets to cure multiple ARDs. Based on the analysis, an online tool named as 'ARDnet' has been developed to construct and demonstrate ARD interactions at the level of PPI, ARDs and ARDs protein interaction, ARDs pathway interaction and drug-target interaction. The tool is freely made available at http://genomeinformatics.dtu.ac.in/ARDNet/Index.html. Copyright © 2017 Elsevier B.V. All rights reserved.

PAINT: a promoter analysis and interaction network generation tool for gene regulatory network identification.

PubMed

Vadigepalli, Rajanikanth; Chakravarthula, Praveen; Zak, Daniel E; Schwaber, James S; Gonye, Gregory E

2003-01-01

We have developed a bioinformatics tool named PAINT that automates the promoter analysis of a given set of genes for the presence of transcription factor binding sites. Based on coincidence of regulatory sites, this tool produces an interaction matrix that represents a candidate transcriptional regulatory network. This tool currently consists of (1) a database of promoter sequences of known or predicted genes in the Ensembl annotated mouse genome database, (2) various modules that can retrieve and process the promoter sequences for binding sites of known transcription factors, and (3) modules for visualization and analysis of the resulting set of candidate network connections. This information provides a substantially pruned list of genes and transcription factors that can be examined in detail in further experimental studies on gene regulation. Also, the candidate network can be incorporated into network identification methods in the form of constraints on feasible structures in order to render the algorithms tractable for large-scale systems. The tool can also produce output in various formats suitable for use in external visualization and analysis software. In this manuscript, PAINT is demonstrated in two case studies involving analysis of differentially regulated genes chosen from two microarray data sets. The first set is from a neuroblastoma N1E-115 cell differentiation experiment, and the second set is from neuroblastoma N1E-115 cells at different time intervals following exposure to neuropeptide angiotensin II. PAINT is available for use as an agent in BioSPICE simulation and analysis framework (www.biospice.org), and can also be accessed via a WWW interface at www.dbi.tju.edu/dbi/tools/paint/.

Meta-analytically informed network analysis of resting state FMRI reveals hyperconnectivity in an introspective socio-affective network in depression.

PubMed

Schilbach, Leonhard; Müller, Veronika I; Hoffstaedter, Felix; Clos, Mareike; Goya-Maldonado, Roberto; Gruber, Oliver; Eickhoff, Simon B

2014-01-01

Alterations of social cognition and dysfunctional interpersonal expectations are thought to play an important role in the etiology of depression and have, thus, become a key target of psychotherapeutic interventions. The underlying neurobiology, however, remains elusive. Based upon the idea of a close link between affective and introspective processes relevant for social interactions and alterations thereof in states of depression, we used a meta-analytically informed network analysis to investigate resting-state functional connectivity in an introspective socio-affective (ISA) network in individuals with and without depression. Results of our analysis demonstrate significant differences between the groups with depressed individuals showing hyperconnectivity of the ISA network. These findings demonstrate that neurofunctional alterations exist in individuals with depression in a neural network relevant for introspection and socio-affective processing, which may contribute to the interpersonal difficulties that are linked to depressive symptomatology.

Meta-Analytically Informed Network Analysis of Resting State fMRI Reveals Hyperconnectivity in an Introspective Socio-Affective Network in Depression

PubMed Central

Schilbach, Leonhard; Müller, Veronika I.; Hoffstaedter, Felix; Clos, Mareike; Goya-Maldonado, Roberto

2014-01-01

Alterations of social cognition and dysfunctional interpersonal expectations are thought to play an important role in the etiology of depression and have, thus, become a key target of psychotherapeutic interventions. The underlying neurobiology, however, remains elusive. Based upon the idea of a close link between affective and introspective processes relevant for social interactions and alterations thereof in states of depression, we used a meta-analytically informed network analysis to investigate resting-state functional connectivity in an introspective socio-affective (ISA) network in individuals with and without depression. Results of our analysis demonstrate significant differences between the groups with depressed individuals showing hyperconnectivity of the ISA network. These findings demonstrate that neurofunctional alterations exist in individuals with depression in a neural network relevant for introspection and socio-affective processing, which may contribute to the interpersonal difficulties that are linked to depressive symptomatology. PMID:24759619

Visualizing collaborative electronic health record usage for hospitalized patients with heart failure.

PubMed

Soulakis, Nicholas D; Carson, Matthew B; Lee, Young Ji; Schneider, Daniel H; Skeehan, Connor T; Scholtens, Denise M

2015-03-01

To visualize and describe collaborative electronic health record (EHR) usage for hospitalized patients with heart failure. We identified records of patients with heart failure and all associated healthcare provider record usage through queries of the Northwestern Medicine Enterprise Data Warehouse. We constructed a network by equating access and updates of a patient's EHR to a provider-patient interaction. We then considered shared patient record access as the basis for a second network that we termed the provider collaboration network. We calculated network statistics, the modularity of provider interactions, and provider cliques. We identified 548 patient records accessed by 5113 healthcare providers in 2012. The provider collaboration network had 1504 nodes and 83 998 edges. We identified 7 major provider collaboration modules. Average clique size was 87.9 providers. We used a graph database to demonstrate an ad hoc query of our provider-patient network. Our analysis suggests a large number of healthcare providers across a wide variety of professions access records of patients with heart failure during their hospital stay. This shared record access tends to take place not only in a pairwise manner but also among large groups of providers. EHRs encode valuable interactions, implicitly or explicitly, between patients and providers. Network analysis provided strong evidence of multidisciplinary record access of patients with heart failure across teams of 100+ providers. Further investigation may lead to clearer understanding of how record access information can be used to strategically guide care coordination for patients hospitalized for heart failure. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association.

Unified functional network and nonlinear time series analysis for complex systems science: The pyunicorn package

NASA Astrophysics Data System (ADS)

Donges, Jonathan; Heitzig, Jobst; Beronov, Boyan; Wiedermann, Marc; Runge, Jakob; Feng, Qing Yi; Tupikina, Liubov; Stolbova, Veronika; Donner, Reik; Marwan, Norbert; Dijkstra, Henk; Kurths, Jürgen

2016-04-01

We introduce the pyunicorn (Pythonic unified complex network and recurrence analysis toolbox) open source software package for applying and combining modern methods of data analysis and modeling from complex network theory and nonlinear time series analysis. pyunicorn is a fully object-oriented and easily parallelizable package written in the language Python. It allows for the construction of functional networks such as climate networks in climatology or functional brain networks in neuroscience representing the structure of statistical interrelationships in large data sets of time series and, subsequently, investigating this structure using advanced methods of complex network theory such as measures and models for spatial networks, networks of interacting networks, node-weighted statistics, or network surrogates. Additionally, pyunicorn provides insights into the nonlinear dynamics of complex systems as recorded in uni- and multivariate time series from a non-traditional perspective by means of recurrence quantification analysis, recurrence networks, visibility graphs, and construction of surrogate time series. The range of possible applications of the library is outlined, drawing on several examples mainly from the field of climatology. pyunicorn is available online at https://github.com/pik-copan/pyunicorn. Reference: J.F. Donges, J. Heitzig, B. Beronov, M. Wiedermann, J. Runge, Q.-Y. Feng, L. Tupikina, V. Stolbova, R.V. Donner, N. Marwan, H.A. Dijkstra, and J. Kurths, Unified functional network and nonlinear time series analysis for complex systems science: The pyunicorn package, Chaos 25, 113101 (2015), DOI: 10.1063/1.4934554, Preprint: arxiv.org:1507.01571 [physics.data-an].

Can Multilayer Networks Advance Animal Behavior Research?

PubMed

Silk, Matthew J; Finn, Kelly R; Porter, Mason A; Pinter-Wollman, Noa

2018-06-01

Interactions among individual animals - and between these individuals and their environment - yield complex, multifaceted systems. The development of multilayer network analysis offers a promising new approach for studying animal social behavior and its relation to eco-evolutionary dynamics. Copyright © 2018 Elsevier Ltd. All rights reserved.

Analysis of the dynamic co-expression network of heart regeneration in the zebrafish

PubMed Central

Rodius, Sophie; Androsova, Ganna; Götz, Lou; Liechti, Robin; Crespo, Isaac; Merz, Susanne; Nazarov, Petr V.; de Klein, Niek; Jeanty, Céline; González-Rosa, Juan M.; Muller, Arnaud; Bernardin, Francois; Niclou, Simone P.; Vallar, Laurent; Mercader, Nadia; Ibberson, Mark; Xenarios, Ioannis; Azuaje, Francisco

2016-01-01

The zebrafish has the capacity to regenerate its heart after severe injury. While the function of a few genes during this process has been studied, we are far from fully understanding how genes interact to coordinate heart regeneration. To enable systematic insights into this phenomenon, we generated and integrated a dynamic co-expression network of heart regeneration in the zebrafish and linked systems-level properties to the underlying molecular events. Across multiple post-injury time points, the network displays topological attributes of biological relevance. We show that regeneration steps are mediated by modules of transcriptionally coordinated genes, and by genes acting as network hubs. We also established direct associations between hubs and validated drivers of heart regeneration with murine and human orthologs. The resulting models and interactive analysis tools are available at http://infused.vital-it.ch. Using a worked example, we demonstrate the usefulness of this unique open resource for hypothesis generation and in silico screening for genes involved in heart regeneration. PMID:27241320

Spatial fingerprints of community structure in human interaction network for an extensive set of large-scale regions.

PubMed

Kallus, Zsófia; Barankai, Norbert; Szüle, János; Vattay, Gábor

2015-01-01

Human interaction networks inferred from country-wide telephone activity recordings were recently used to redraw political maps by projecting their topological partitions into geographical space. The results showed remarkable spatial cohesiveness of the network communities and a significant overlap between the redrawn and the administrative borders. Here we present a similar analysis based on one of the most popular online social networks represented by the ties between more than 5.8 million of its geo-located users. The worldwide coverage of their measured activity allowed us to analyze the large-scale regional subgraphs of entire continents and an extensive set of examples for single countries. We present results for North and South America, Europe and Asia. In our analysis we used the well-established method of modularity clustering after an aggregation of the individual links into a weighted graph connecting equal-area geographical pixels. Our results show fingerprints of both of the opposing forces of dividing local conflicts and of uniting cross-cultural trends of globalization.

Analysis of the dynamic co-expression network of heart regeneration in the zebrafish

NASA Astrophysics Data System (ADS)

Rodius, Sophie; Androsova, Ganna; Götz, Lou; Liechti, Robin; Crespo, Isaac; Merz, Susanne; Nazarov, Petr V.; de Klein, Niek; Jeanty, Céline; González-Rosa, Juan M.; Muller, Arnaud; Bernardin, Francois; Niclou, Simone P.; Vallar, Laurent; Mercader, Nadia; Ibberson, Mark; Xenarios, Ioannis; Azuaje, Francisco

2016-05-01

The zebrafish has the capacity to regenerate its heart after severe injury. While the function of a few genes during this process has been studied, we are far from fully understanding how genes interact to coordinate heart regeneration. To enable systematic insights into this phenomenon, we generated and integrated a dynamic co-expression network of heart regeneration in the zebrafish and linked systems-level properties to the underlying molecular events. Across multiple post-injury time points, the network displays topological attributes of biological relevance. We show that regeneration steps are mediated by modules of transcriptionally coordinated genes, and by genes acting as network hubs. We also established direct associations between hubs and validated drivers of heart regeneration with murine and human orthologs. The resulting models and interactive analysis tools are available at http://infused.vital-it.ch. Using a worked example, we demonstrate the usefulness of this unique open resource for hypothesis generation and in silico screening for genes involved in heart regeneration.

A network analysis of cofactor-protein interactions for analyzing associations between human nutrition and diseases

PubMed Central

Scott-Boyer, Marie Pier; Lacroix, Sébastien; Scotti, Marco; Morine, Melissa J.; Kaput, Jim; Priami, Corrado

2016-01-01

The involvement of vitamins and other micronutrients in intermediary metabolism was elucidated in the mid 1900’s at the level of individual biochemical reactions. Biochemical pathways remain the foundational knowledgebase for understanding how micronutrient adequacy modulates health in all life stages. Current daily recommended intakes were usually established on the basis of the association of a single nutrient to a single, most sensitive adverse effect and thus neglect interdependent and pleiotropic effects of micronutrients on biological systems. Hence, the understanding of the impact of overt or sub-clinical nutrient deficiencies on biological processes remains incomplete. Developing a more complete view of the role of micronutrients and their metabolic products in protein-mediated reactions is of importance. We thus integrated and represented cofactor-protein interaction data from multiple and diverse sources into a multi-layer network representation that links cofactors, cofactor-interacting proteins, biological processes, and diseases. Network representation of this information is a key feature of the present analysis and enables the integration of data from individual biochemical reactions and protein-protein interactions into a systems view, which may guide strategies for targeted nutritional interventions aimed at improving health and preventing diseases. PMID:26777674

Analysis of continuous-time switching networks

NASA Astrophysics Data System (ADS)

Edwards, R.

2000-11-01

Models of a number of biological systems, including gene regulation and neural networks, can be formulated as switching networks, in which the interactions between the variables depend strongly on thresholds. An idealized class of such networks in which the switching takes the form of Heaviside step functions but variables still change continuously in time has been proposed as a useful simplification to gain analytic insight. These networks, called here Glass networks after their originator, are simple enough mathematically to allow significant analysis without restricting the range of dynamics found in analogous smooth systems. A number of results have been obtained before, particularly regarding existence and stability of periodic orbits in such networks, but important cases were not considered. Here we present a coherent method of analysis that summarizes previous work and fills in some of the gaps as well as including some new results. Furthermore, we apply this analysis to a number of examples, including surprising long and complex limit cycles involving sequences of hundreds of threshold transitions. Finally, we show how the above methods can be extended to investigate aperiodic behaviour in specific networks, though a complete analysis will have to await new results in matrix theory and symbolic dynamics.

Ecological network analysis for a virtual water network.

PubMed

Fang, Delin; Chen, Bin

2015-06-02

The notions of virtual water flows provide important indicators to manifest the water consumption and allocation between different sectors via product transactions. However, the configuration of virtual water network (VWN) still needs further investigation to identify the water interdependency among different sectors as well as the network efficiency and stability in a socio-economic system. Ecological network analysis is chosen as a useful tool to examine the structure and function of VWN and the interactions among its sectors. A balance analysis of efficiency and redundancy is also conducted to describe the robustness (RVWN) of VWN. Then, network control analysis and network utility analysis are performed to investigate the dominant sectors and pathways for virtual water circulation and the mutual relationships between pairwise sectors. A case study of the Heihe River Basin in China shows that the balance between efficiency and redundancy is situated on the left side of the robustness curve with less efficiency and higher redundancy. The forestation, herding and fishing sectors and industrial sectors are found to be the main controllers. The network tends to be more mutualistic and synergic, though some competitive relationships that weaken the virtual water circulation still exist.

A systems biology model of the regulatory network in Populus leaves reveals interacting regulators and conserved regulation

PubMed Central

2011-01-01

Background Green plant leaves have always fascinated biologists as hosts for photosynthesis and providers of basic energy to many food webs. Today, comprehensive databases of gene expression data enable us to apply increasingly more advanced computational methods for reverse-engineering the regulatory network of leaves, and to begin to understand the gene interactions underlying complex emergent properties related to stress-response and development. These new systems biology methods are now also being applied to organisms such as Populus, a woody perennial tree, in order to understand the specific characteristics of these species. Results We present a systems biology model of the regulatory network of Populus leaves. The network is reverse-engineered from promoter information and expression profiles of leaf-specific genes measured over a large set of conditions related to stress and developmental. The network model incorporates interactions between regulators, such as synergistic and competitive relationships, by evaluating increasingly more complex regulatory mechanisms, and is therefore able to identify new regulators of leaf development not found by traditional genomics methods based on pair-wise expression similarity. The approach is shown to explain available gene function information and to provide robust prediction of expression levels in new data. We also use the predictive capability of the model to identify condition-specific regulation as well as conserved regulation between Populus and Arabidopsis. Conclusions We outline a computationally inferred model of the regulatory network of Populus leaves, and show how treating genes as interacting, rather than individual, entities identifies new regulators compared to traditional genomics analysis. Although systems biology models should be used with care considering the complexity of regulatory programs and the limitations of current genomics data, methods describing interactions can provide hypotheses about the underlying cause of emergent properties and are needed if we are to identify target genes other than those constituting the "low hanging fruit" of genomic analysis. PMID:21232107

Sig2BioPAX: Java tool for converting flat files to BioPAX Level 3 format.

PubMed

Webb, Ryan L; Ma'ayan, Avi

2011-03-21

The World Wide Web plays a critical role in enabling molecular, cell, systems and computational biologists to exchange, search, visualize, integrate, and analyze experimental data. Such efforts can be further enhanced through the development of semantic web concepts. The semantic web idea is to enable machines to understand data through the development of protocol free data exchange formats such as Resource Description Framework (RDF) and the Web Ontology Language (OWL). These standards provide formal descriptors of objects, object properties and their relationships within a specific knowledge domain. However, the overhead of converting datasets typically stored in data tables such as Excel, text or PDF into RDF or OWL formats is not trivial for non-specialists and as such produces a barrier to seamless data exchange between researchers, databases and analysis tools. This problem is particularly of importance in the field of network systems biology where biochemical interactions between genes and their protein products are abstracted to networks. For the purpose of converting biochemical interactions into the BioPAX format, which is the leading standard developed by the computational systems biology community, we developed an open-source command line tool that takes as input tabular data describing different types of molecular biochemical interactions. The tool converts such interactions into the BioPAX level 3 OWL format. We used the tool to convert several existing and new mammalian networks of protein interactions, signalling pathways, and transcriptional regulatory networks into BioPAX. Some of these networks were deposited into PathwayCommons, a repository for consolidating and organizing biochemical networks. The software tool Sig2BioPAX is a resource that enables experimental and computational systems biologists to contribute their identified networks and pathways of molecular interactions for integration and reuse with the rest of the research community.

Network inference reveals novel connections in pathways regulating growth and defense in the yeast salt response.

PubMed

MacGilvray, Matthew E; Shishkova, Evgenia; Chasman, Deborah; Place, Michael; Gitter, Anthony; Coon, Joshua J; Gasch, Audrey P

2018-05-01

Cells respond to stressful conditions by coordinating a complex, multi-faceted response that spans many levels of physiology. Much of the response is coordinated by changes in protein phosphorylation. Although the regulators of transcriptome changes during stress are well characterized in Saccharomyces cerevisiae, the upstream regulatory network controlling protein phosphorylation is less well dissected. Here, we developed a computational approach to infer the signaling network that regulates phosphorylation changes in response to salt stress. We developed an approach to link predicted regulators to groups of likely co-regulated phospho-peptides responding to stress, thereby creating new edges in a background protein interaction network. We then use integer linear programming (ILP) to integrate wild type and mutant phospho-proteomic data and predict the network controlling stress-activated phospho-proteomic changes. The network we inferred predicted new regulatory connections between stress-activated and growth-regulating pathways and suggested mechanisms coordinating metabolism, cell-cycle progression, and growth during stress. We confirmed several network predictions with co-immunoprecipitations coupled with mass-spectrometry protein identification and mutant phospho-proteomic analysis. Results show that the cAMP-phosphodiesterase Pde2 physically interacts with many stress-regulated transcription factors targeted by PKA, and that reduced phosphorylation of those factors during stress requires the Rck2 kinase that we show physically interacts with Pde2. Together, our work shows how a high-quality computational network model can facilitate discovery of new pathway interactions during osmotic stress.

Robust co-regulation of tyrosine phosphorylation sites on proteins reveals novel protein interactions†

PubMed Central

Naegle, Kristen M.; White, Forest M.; Lauffenburger, Douglas A.; Yaffe, Michael B.

2012-01-01

Cell signaling networks propagate information from extracellular cues via dynamic modulation of protein–protein interactions in a context-dependent manner. Networks based on receptor tyrosine kinases (RTKs), for example, phosphorylate intracellular proteins in response to extracellular ligands, resulting in dynamic protein–protein interactions that drive phenotypic changes. Most commonly used methods for discovering these protein–protein interactions, however, are optimized for detecting stable, longer-lived complexes, rather than the type of transient interactions that are essential components of dynamic signaling networks such as those mediated by RTKs. Substrate phosphorylation downstream of RTK activation modifies substrate activity and induces phospho-specific binding interactions, resulting in the formation of large transient macromolecular signaling complexes. Since protein complex formation should follow the trajectory of events that drive it, we reasoned that mining phosphoproteomic datasets for highly similar dynamic behavior of measured phosphorylation sites on different proteins could be used to predict novel, transient protein–protein interactions that had not been previously identified. We applied this method to explore signaling events downstream of EGFR stimulation. Our computational analysis of robustly co-regulated phosphorylation sites, based on multiple clustering analysis of quantitative time-resolved mass-spectrometry phosphoproteomic data, not only identified known sitewise-specific recruitment of proteins to EGFR, but also predicted novel, a priori interactions. A particularly intriguing prediction of EGFR interaction with the cytoskeleton-associated protein PDLIM1 was verified within cells using co-immunoprecipitation and in situ proximity ligation assays. Our approach thus offers a new way to discover protein–protein interactions in a dynamic context- and phosphorylation site-specific manner. PMID:22851037

Vertical Interaction in Open Software Engineering Communities

DTIC Science & Technology

2009-03-01

Program in CASOS (NSF,DGE-9972762), the Office of Naval Research under Dynamic Network Analysis program (N00014-02-1-0973, the Air Force Office of...W91WAW07C0063) for research in the area of dynamic network analysis. Additional support was provided by CASOS - the center for Computational Analysis of Social...methods across the domain. For a given project, de - velopers can choose from dozens of models, tools, platforms, and languages for specification, design

Integration of Structural Dynamics and Molecular Evolution via Protein Interaction Networks: A New Era in Genomic Medicine

PubMed Central

Kumar, Avishek; Butler, Brandon M.; Kumar, Sudhir; Ozkan, S. Banu

2016-01-01

Summary Sequencing technologies are revealing many new non-synonymous single nucleotide variants (nsSNVs) in each personal exome. To assess their functional impacts, comparative genomics is frequently employed to predict if they are benign or not. However, evolutionary analysis alone is insufficient, because it misdiagnoses many disease-associated nsSNVs, such as those at positions involved in protein interfaces, and because evolutionary predictions do not provide mechanistic insights into functional change or loss. Structural analyses can aid in overcoming both of these problems by incorporating conformational dynamics and allostery in nSNV diagnosis. Finally, protein-protein interaction networks using systems-level methodologies shed light onto disease etiology and pathogenesis. Bridging these network approaches with structurally resolved protein interactions and dynamics will advance genomic medicine. PMID:26684487

What's Next in Complex Networks? Capturing the Concept of Attacking Play in Invasive Team Sports.

PubMed

Ramos, João; Lopes, Rui J; Araújo, Duarte

2018-01-01

The evolution of performance analysis within sports sciences is tied to technology development and practitioner demands. However, how individual and collective patterns self-organize and interact in invasive team sports remains elusive. Social network analysis has been recently proposed to resolve some aspects of this problem, and has proven successful in capturing collective features resulting from the interactions between team members as well as a powerful communication tool. Despite these advances, some fundamental team sports concepts such as an attacking play have not been properly captured by the more common applications of social network analysis to team sports performance. In this article, we propose a novel approach to team sports performance centered on sport concepts, namely that of an attacking play. Network theory and tools including temporal and bipartite or multilayered networks were used to capture this concept. We put forward eight questions directly related to team performance to discuss how common pitfalls in the use of network tools for capturing sports concepts can be avoided. Some answers are advanced in an attempt to be more precise in the description of team dynamics and to uncover other metrics directly applied to sport concepts, such as the structure and dynamics of attacking plays. Finally, we propose that, at this stage of knowledge, it may be advantageous to build up from fundamental sport concepts toward complex network theory and tools, and not the other way around.

IntNetDB v1.0: an integrated protein-protein interaction network database generated by a probabilistic model

PubMed Central

Xia, Kai; Dong, Dong; Han, Jing-Dong J

2006-01-01

Background Although protein-protein interaction (PPI) networks have been explored by various experimental methods, the maps so built are still limited in coverage and accuracy. To further expand the PPI network and to extract more accurate information from existing maps, studies have been carried out to integrate various types of functional relationship data. A frequently updated database of computationally analyzed potential PPIs to provide biological researchers with rapid and easy access to analyze original data as a biological network is still lacking. Results By applying a probabilistic model, we integrated 27 heterogeneous genomic, proteomic and functional annotation datasets to predict PPI networks in human. In addition to previously studied data types, we show that phenotypic distances and genetic interactions can also be integrated to predict PPIs. We further built an easy-to-use, updatable integrated PPI database, the Integrated Network Database (IntNetDB) online, to provide automatic prediction and visualization of PPI network among genes of interest. The networks can be visualized in SVG (Scalable Vector Graphics) format for zooming in or out. IntNetDB also provides a tool to extract topologically highly connected network neighborhoods from a specific network for further exploration and research. Using the MCODE (Molecular Complex Detections) algorithm, 190 such neighborhoods were detected among all the predicted interactions. The predicted PPIs can also be mapped to worm, fly and mouse interologs. Conclusion IntNetDB includes 180,010 predicted protein-protein interactions among 9,901 human proteins and represents a useful resource for the research community. Our study has increased prediction coverage by five-fold. IntNetDB also provides easy-to-use network visualization and analysis tools that allow biological researchers unfamiliar with computational biology to access and analyze data over the internet. The web interface of IntNetDB is freely accessible at . Visualization requires Mozilla version 1.8 (or higher) or Internet Explorer with installation of SVGviewer. PMID:17112386

Understanding ZHENG in traditional Chinese medicine in the context of neuro-endocrine-immune network.

PubMed

Li, S; Zhang, Z Q; Wu, L J; Zhang, X G; Li, Y D; Wang, Y Y

2007-01-01

Traditional Chinese medicine uses ZHENG as the key pathological principle to understand the human homeostasis and guide the applications of Chinese herbs. Here, a systems biology approach with the combination of computational analysis and animal experiment is used to investigate this complex issue, ZHENG, in the context of the neuro-endocrine-immune (NEI) system. By using the methods of literature mining, network analysis and topological comparison, it is found that hormones are predominant in the Cold ZHENG network, immune factors are predominant in the Hot ZHENG network, and these two networks are connected by neuro-transmitters. In addition, genes related to Hot ZHENG-related diseases are mainly present in the cytokine-cytokine receptor interaction pathway, whereas genes related to both the Cold-related and Hot-related diseases are linked to the neuroactive ligand-receptor interaction pathway. These computational findings were subsequently verified by experiments on a rat model of collagen-induced arthritis, which indicate that the Cold ZHENG-oriented herbs tend to affect the hub nodes in the Cold ZHENG network, and the Hot ZHENG-oriented herbs tend to affect the hub nodes in the Hot ZHENG network. These investigations demonstrate that the thousand-year-old concept of ZHENG may have a molecular basis with NEI as background.

Development and application of an interaction network ontology for literature mining of vaccine-associated gene-gene interactions.

PubMed

Hur, Junguk; Özgür, Arzucan; Xiang, Zuoshuang; He, Yongqun

2015-01-01

Literature mining of gene-gene interactions has been enhanced by ontology-based name classifications. However, in biomedical literature mining, interaction keywords have not been carefully studied and used beyond a collection of keywords. In this study, we report the development of a new Interaction Network Ontology (INO) that classifies >800 interaction keywords and incorporates interaction terms from the PSI Molecular Interactions (PSI-MI) and Gene Ontology (GO). Using INO-based literature mining results, a modified Fisher's exact test was established to analyze significantly over- and under-represented enriched gene-gene interaction types within a specific area. Such a strategy was applied to study the vaccine-mediated gene-gene interactions using all PubMed abstracts. The Vaccine Ontology (VO) and INO were used to support the retrieval of vaccine terms and interaction keywords from the literature. INO is aligned with the Basic Formal Ontology (BFO) and imports terms from 10 other existing ontologies. Current INO includes 540 terms. In terms of interaction-related terms, INO imports and aligns PSI-MI and GO interaction terms and includes over 100 newly generated ontology terms with 'INO_' prefix. A new annotation property, 'has literature mining keywords', was generated to allow the listing of different keywords mapping to the interaction types in INO. Using all PubMed documents published as of 12/31/2013, approximately 266,000 vaccine-associated documents were identified, and a total of 6,116 gene-pairs were associated with at least one INO term. Out of 78 INO interaction terms associated with at least five gene-pairs of the vaccine-associated sub-network, 14 terms were significantly over-represented (i.e., more frequently used) and 17 under-represented based on our modified Fisher's exact test. These over-represented and under-represented terms share some common top-level terms but are distinct at the bottom levels of the INO hierarchy. The analysis of these interaction types and their associated gene-gene pairs uncovered many scientific insights. INO provides a novel approach for defining hierarchical interaction types and related keywords for literature mining. The ontology-based literature mining, in combination with an INO-based statistical interaction enrichment test, provides a new platform for efficient mining and analysis of topic-specific gene interaction networks.

The spreading of opposite opinions on online social networks with authoritative nodes

NASA Astrophysics Data System (ADS)

Yan, Shu; Tang, Shaoting; Pei, Sen; Jiang, Shijin; Zhang, Xiao; Ding, Wenrui; Zheng, Zhiming

2013-09-01

The study of opinion dynamics, such as spreading and controlling of rumors, has become an important issue on social networks. Numerous models have been devised to describe this process, including epidemic models and spin models, which mainly focus on how opinions spread and interact with each other, respectively. In this paper, we propose a model that combines the spreading stage and the interaction stage for opinions to illustrate the process of dispelling a rumor. Moreover, we set up authoritative nodes, which disseminate positive opinion to counterbalance the negative opinion prevailing on online social networking sites. With analysis of the relationship among positive opinion proportion, opinion strength and the density of authoritative nodes in networks with different topologies, we demonstrate that the positive opinion proportion grows with the density of authoritative nodes until the positive opinion prevails in the entire network. In particular, the relationship is linear in homogeneous topologies. Besides, it is also noteworthy that initial locations of the negative opinion source and authoritative nodes do not influence positive opinion proportion in homogeneous networks but have a significant impact on heterogeneous networks. The results are verified by numerical simulations and are helpful to understand the mechanism of two different opinions interacting with each other on online social networking sites.

Framework based on communicability and flow to analyze complex network dynamics

NASA Astrophysics Data System (ADS)

Gilson, M.; Kouvaris, N. E.; Deco, G.; Zamora-López, G.

2018-05-01

Graph theory constitutes a widely used and established field providing powerful tools for the characterization of complex networks. The intricate topology of networks can also be investigated by means of the collective dynamics observed in the interactions of self-sustained oscillations (synchronization patterns) or propagationlike processes such as random walks. However, networks are often inferred from real-data-forming dynamic systems, which are different from those employed to reveal their topological characteristics. This stresses the necessity for a theoretical framework dedicated to the mutual relationship between the structure and dynamics in complex networks, as the two sides of the same coin. Here we propose a rigorous framework based on the network response over time (i.e., Green function) to study interactions between nodes across time. For this purpose we define the flow that describes the interplay between the network connectivity and external inputs. This multivariate measure relates to the concepts of graph communicability and the map equation. We illustrate our theory using the multivariate Ornstein-Uhlenbeck process, which describes stable and non-conservative dynamics, but the formalism can be adapted to other local dynamics for which the Green function is known. We provide applications to classical network examples, such as small-world ring and hierarchical networks. Our theory defines a comprehensive framework that is canonically related to directed and weighted networks, thus paving a way to revise the standards for network analysis, from the pairwise interactions between nodes to the global properties of networks including community detection.

A Combined Computational and Genetic Approach Uncovers Network Interactions of the Cyanobacterial Circadian Clock.

PubMed

Boyd, Joseph S; Cheng, Ryan R; Paddock, Mark L; Sancar, Cigdem; Morcos, Faruck; Golden, Susan S

2016-09-15

Two-component systems (TCS) that employ histidine kinases (HK) and response regulators (RR) are critical mediators of cellular signaling in bacteria. In the model cyanobacterium Synechococcus elongatus PCC 7942, TCSs control global rhythms of transcription that reflect an integration of time information from the circadian clock with a variety of cellular and environmental inputs. The HK CikA and the SasA/RpaA TCS transduce time information from the circadian oscillator to modulate downstream cellular processes. Despite immense progress in understanding of the circadian clock itself, many of the connections between the clock and other cellular signaling systems have remained enigmatic. To narrow the search for additional TCS components that connect to the clock, we utilized direct-coupling analysis (DCA), a statistical analysis of covariant residues among related amino acid sequences, to infer coevolution of new and known clock TCS components. DCA revealed a high degree of interaction specificity between SasA and CikA with RpaA, as expected, but also with the phosphate-responsive response regulator SphR. Coevolutionary analysis also predicted strong specificity between RpaA and a previously undescribed kinase, HK0480 (herein CikB). A knockout of the gene for CikB (cikB) in a sasA cikA null background eliminated the RpaA phosphorylation and RpaA-controlled transcription that is otherwise present in that background and suppressed cell elongation, supporting the notion that CikB is an interactor with RpaA and the clock network. This study demonstrates the power of DCA to identify subnetworks and key interactions in signaling pathways and of combinatorial mutagenesis to explore the phenotypic consequences. Such a combined strategy is broadly applicable to other prokaryotic systems. Signaling networks are complex and extensive, comprising multiple integrated pathways that respond to cellular and environmental cues. A TCS interaction model, based on DCA, independently confirmed known interactions and revealed a core set of subnetworks within the larger HK-RR set. We validated high-scoring candidate proteins via combinatorial genetics, demonstrating that DCA can be utilized to reduce the search space of complex protein networks and to infer undiscovered specific interactions for signaling proteins in vivo Significantly, new interactions that link circadian response to cell division and fitness in a light/dark cycle were uncovered. The combined analysis also uncovered a more basic core clock, illustrating the synergy and applicability of a combined computational and genetic approach for investigating prokaryotic signaling networks. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

CerebralWeb: a Cytoscape.js plug-in to visualize networks stratified by subcellular localization.

PubMed

Frias, Silvia; Bryan, Kenneth; Brinkman, Fiona S L; Lynn, David J

2015-01-01

CerebralWeb is a light-weight JavaScript plug-in that extends Cytoscape.js to enable fast and interactive visualization of molecular interaction networks stratified based on subcellular localization or other user-supplied annotation. The application is designed to be easily integrated into any website and is configurable to support customized network visualization. CerebralWeb also supports the automatic retrieval of Cerebral-compatible localizations for human, mouse and bovine genes via a web service and enables the automated parsing of Cytoscape compatible XGMML network files. CerebralWeb currently supports embedded network visualization on the InnateDB (www.innatedb.com) and Allergy and Asthma Portal (allergen.innatedb.com) database and analysis resources. Database tool URL: http://www.innatedb.com/CerebralWeb © The Author(s) 2015. Published by Oxford University Press.

Geometric control of capillary architecture via cell-matrix mechanical interactions.

PubMed

Sun, Jian; Jamilpour, Nima; Wang, Fei-Yue; Wong, Pak Kin

2014-03-01

Capillary morphogenesis is a multistage, multicellular activity that plays a pivotal role in various developmental and pathological situations. In-depth understanding of the regulatory mechanism along with the capability of controlling the morphogenic process will have direct implications on tissue engineering and therapeutic angiogenesis. Extensive research has been devoted to elucidate the biochemical factors that regulate capillary morphogenesis. The roles of geometric confinement and cell-matrix mechanical interactions on the capillary architecture, nevertheless, remain largely unknown. Here, we show geometric control of endothelial network topology by creating physical confinements with microfabricated fences and wells. Decreasing the thickness of the matrix also results in comparable modulation of the network architecture, supporting the boundary effect is mediated mechanically. The regulatory role of cell-matrix mechanical interaction on the network topology is further supported by alternating the matrix stiffness by a cell-inert PEG-dextran hydrogel. Furthermore, reducing the cell traction force with a Rho-associated protein kinase inhibitor diminishes the boundary effect. Computational biomechanical analysis delineates the relationship between geometric confinement and cell-matrix mechanical interaction. Collectively, these results reveal a mechanoregulation scheme of endothelial cells to regulate the capillary network architecture via cell-matrix mechanical interactions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Do cancer proteins really interact strongly in the human protein-protein interaction network?

PubMed

Xia, Junfeng; Sun, Jingchun; Jia, Peilin; Zhao, Zhongming

2011-06-01

Protein-protein interaction (PPI) network analysis has been widely applied in the investigation of the mechanisms of diseases, especially cancer. Recent studies revealed that cancer proteins tend to interact more strongly than other categories of proteins, even essential proteins, in the human interactome. However, it remains unclear whether this observation was introduced by the bias towards more cancer studies in humans. Here, we examined this important issue by uniquely comparing network characteristics of cancer proteins with three other sets of proteins in four organisms, three of which (fly, worm, and yeast) whose interactomes are essentially not biased towards cancer or other diseases. We confirmed that cancer proteins had stronger connectivity, shorter distance, and larger betweenness centrality than non-cancer disease proteins, essential proteins, and control proteins. Our statistical evaluation indicated that such observations were overall unlikely attributed to random events. Considering the large size and high quality of the PPI data in the four organisms, the conclusion that cancer proteins interact strongly in the PPI networks is reliable and robust. This conclusion suggests that perturbation of cancer proteins might cause major changes of cellular systems and result in abnormal cell function leading to cancer. © 2011 Elsevier Ltd. All rights reserved.

Do cancer proteins really interact strongly in the human protein-protein interaction network?

PubMed Central

Xia, Junfeng; Sun, Jingchun; Jia, Peilin; Zhao, Zhongming

2011-01-01

Protein-protein interaction (PPI) network analysis has been widely applied in the investigation of the mechanisms of diseases, especially cancer. Recent studies revealed that cancer proteins tend to interact more strongly than other categories of proteins, even essential proteins, in the human interactome. However, it remains unclear whether this observation was introduced by the bias towards more cancer studies in humans. Here, we examined this important issue by uniquely comparing network characteristics of cancer proteins with three other sets of proteins in four organisms, three of which (fly, worm, and yeast) whose interactomes are essentially not biased towards cancer or other diseases. We confirmed that cancer proteins had stronger connectivity, shorter distance, and larger betweenness centrality than non-cancer disease proteins, essential proteins, and control proteins. Our statistical evaluation indicated that such observations were overall unlikely attributed to random events. Considering the large size and high quality of the PPI data in the four organisms, the conclusion that cancer proteins interact strongly in the PPI networks is reliable and robust. This conclusion suggests that perturbation of cancer proteins might cause major changes of cellular systems and result in abnormal cell function leading to cancer. PMID:21666777

Interaction mining and skill-dependent recommendations for multi-objective team composition

PubMed Central

Dorn, Christoph; Skopik, Florian; Schall, Daniel; Dustdar, Schahram

2011-01-01

Web-based collaboration and virtual environments supported by various Web 2.0 concepts enable the application of numerous monitoring, mining and analysis tools to study human interactions and team formation processes. The composition of an effective team requires a balance between adequate skill fulfillment and sufficient team connectivity. The underlying interaction structure reflects social behavior and relations of individuals and determines to a large degree how well people can be expected to collaborate. In this paper we address an extended team formation problem that does not only require direct interactions to determine team connectivity but additionally uses implicit recommendations of collaboration partners to support even sparsely connected networks. We provide two heuristics based on Genetic Algorithms and Simulated Annealing for discovering efficient team configurations that yield the best trade-off between skill coverage and team connectivity. Our self-adjusting mechanism aims to discover the best combination of direct interactions and recommendations when deriving connectivity. We evaluate our approach based on multiple configurations of a simulated collaboration network that features close resemblance to real world expert networks. We demonstrate that our algorithm successfully identifies efficient team configurations even when removing up to 40% of experts from various social network configurations. PMID:22298939

Protein function prediction using neighbor relativity in protein-protein interaction network.

PubMed

Moosavi, Sobhan; Rahgozar, Masoud; Rahimi, Amir

2013-04-01

There is a large gap between the number of discovered proteins and the number of functionally annotated ones. Due to the high cost of determining protein function by wet-lab research, function prediction has become a major task for computational biology and bioinformatics. Some researches utilize the proteins interaction information to predict function for un-annotated proteins. In this paper, we propose a novel approach called "Neighbor Relativity Coefficient" (NRC) based on interaction network topology which estimates the functional similarity between two proteins. NRC is calculated for each pair of proteins based on their graph-based features including distance, common neighbors and the number of paths between them. In order to ascribe function to an un-annotated protein, NRC estimates a weight for each neighbor to transfer its annotation to the unknown protein. Finally, the unknown protein will be annotated by the top score transferred functions. We also investigate the effect of using different coefficients for various types of functions. The proposed method has been evaluated on Saccharomyces cerevisiae and Homo sapiens interaction networks. The performance analysis demonstrates that NRC yields better results in comparison with previous protein function prediction approaches that utilize interaction network. Copyright © 2012 Elsevier Ltd. All rights reserved.

Geo-Distinctive Comorbidity Networks of Pediatric Asthma.

PubMed

Shin, Eun Kyong; Shaban-Nejad, Arash

2018-01-01

Most pediatric asthma cases occur in complex interdependencies, exhibiting complex manifestation of multiple symptoms. Studying asthma comorbidities can help to better understand the etiology pathway of the disease. Albeit such relations of co-expressed symptoms and their interactions have been highlighted recently, empirical investigation has not been rigorously applied to pediatric asthma cases. In this study, we use computational network modeling and analysis to reveal the links and associations between commonly co-observed diseases/conditions with asthma among children in Memphis, Tennessee. We present a novel method for geo-parsed comorbidity network analysis to show the distinctive patterns of comorbidity networks in urban and suburban areas in Memphis.

Reliability analysis of interdependent lattices

NASA Astrophysics Data System (ADS)

Limiao, Zhang; Daqing, Li; Pengju, Qin; Bowen, Fu; Yinan, Jiang; Zio, Enrico; Rui, Kang

2016-06-01

Network reliability analysis has drawn much attention recently due to the risks of catastrophic damage in networked infrastructures. These infrastructures are dependent on each other as a result of various interactions. However, most of the reliability analyses of these interdependent networks do not consider spatial constraints, which are found important for robustness of infrastructures including power grid and transport systems. Here we study the reliability properties of interdependent lattices with different ranges of spatial constraints. Our study shows that interdependent lattices with strong spatial constraints are more resilient than interdependent Erdös-Rényi networks. There exists an intermediate range of spatial constraints, at which the interdependent lattices have minimal resilience.

Process-based network decomposition reveals backbone motif structure

PubMed Central

Wang, Guanyu; Du, Chenghang; Chen, Hao; Simha, Rahul; Rong, Yongwu; Xiao, Yi; Zeng, Chen

2010-01-01

A central challenge in systems biology today is to understand the network of interactions among biomolecules and, especially, the organizing principles underlying such networks. Recent analysis of known networks has identified small motifs that occur ubiquitously, suggesting that larger networks might be constructed in the manner of electronic circuits by assembling groups of these smaller modules. Using a unique process-based approach to analyzing such networks, we show for two cell-cycle networks that each of these networks contains a giant backbone motif spanning all the network nodes that provides the main functional response. The backbone is in fact the smallest network capable of providing the desired functionality. Furthermore, the remaining edges in the network form smaller motifs whose role is to confer stability properties rather than provide function. The process-based approach used in the above analysis has additional benefits: It is scalable, analytic (resulting in a single analyzable expression that describes the behavior), and computationally efficient (all possible minimal networks for a biological process can be identified and enumerated). PMID:20498084

TranscriptomeBrowser 3.0: introducing a new compendium of molecular interactions and a new visualization tool for the study of gene regulatory networks.

PubMed

Lepoivre, Cyrille; Bergon, Aurélie; Lopez, Fabrice; Perumal, Narayanan B; Nguyen, Catherine; Imbert, Jean; Puthier, Denis

2012-01-31

Deciphering gene regulatory networks by in silico approaches is a crucial step in the study of the molecular perturbations that occur in diseases. The development of regulatory maps is a tedious process requiring the comprehensive integration of various evidences scattered over biological databases. Thus, the research community would greatly benefit from having a unified database storing known and predicted molecular interactions. Furthermore, given the intrinsic complexity of the data, the development of new tools offering integrated and meaningful visualizations of molecular interactions is necessary to help users drawing new hypotheses without being overwhelmed by the density of the subsequent graph. We extend the previously developed TranscriptomeBrowser database with a set of tables containing 1,594,978 human and mouse molecular interactions. The database includes: (i) predicted regulatory interactions (computed by scanning vertebrate alignments with a set of 1,213 position weight matrices), (ii) potential regulatory interactions inferred from systematic analysis of ChIP-seq experiments, (iii) regulatory interactions curated from the literature, (iv) predicted post-transcriptional regulation by micro-RNA, (v) protein kinase-substrate interactions and (vi) physical protein-protein interactions. In order to easily retrieve and efficiently analyze these interactions, we developed In-teractomeBrowser, a graph-based knowledge browser that comes as a plug-in for Transcriptome-Browser. The first objective of InteractomeBrowser is to provide a user-friendly tool to get new insight into any gene list by providing a context-specific display of putative regulatory and physical interactions. To achieve this, InteractomeBrowser relies on a "cell compartments-based layout" that makes use of a subset of the Gene Ontology to map gene products onto relevant cell compartments. This layout is particularly powerful for visual integration of heterogeneous biological information and is a productive avenue in generating new hypotheses. The second objective of InteractomeBrowser is to fill the gap between interaction databases and dynamic modeling. It is thus compatible with the network analysis software Cytoscape and with the Gene Interaction Network simulation software (GINsim). We provide examples underlying the benefits of this visualization tool for large gene set analysis related to thymocyte differentiation. The InteractomeBrowser plugin is a powerful tool to get quick access to a knowledge database that includes both predicted and validated molecular interactions. InteractomeBrowser is available through the TranscriptomeBrowser framework and can be found at: http://tagc.univ-mrs.fr/tbrowser/. Our database is updated on a regular basis.

Linking disease-associated genes to regulatory networks via promoter organization

PubMed Central

Döhr, S.; Klingenhoff, A.; Maier, H.; de Angelis, M. Hrabé; Werner, T.; Schneider, R.

2005-01-01

Pathway- or disease-associated genes may participate in more than one transcriptional co-regulation network. Such gene groups can be readily obtained by literature analysis or by high-throughput techniques such as microarrays or protein-interaction mapping. We developed a strategy that defines regulatory networks by in silico promoter analysis, finding potentially co-regulated subgroups without a priori knowledge. Pairs of transcription factor binding sites conserved in orthologous genes (vertically) as well as in promoter sequences of co-regulated genes (horizontally) were used as seeds for the development of promoter models representing potential co-regulation. This approach was applied to a Maturity Onset Diabetes of the Young (MODY)-associated gene list, which yielded two models connecting functionally interacting genes within MODY-related insulin/glucose signaling pathways. Additional genes functionally connected to our initial gene list were identified by database searches with these promoter models. Thus, data-driven in silico promoter analysis allowed integrating molecular mechanisms with biological functions of the cell. PMID:15701758

Interactions between neurons in the frontal cortex and hippocampus in cats trained to select reinforcements of different value in conditions of cholinergic deficiency.

PubMed

Dolbakyan, E E; Merzhanova, G Kh

2007-09-01

An operant food-related conditioned reflex was developed in six cats by the "active choice" protocol: short-latency pedal presses were followed by presentation of low-quality reinforcement (bread-meat mix), while long-latency pedal presses were followed by presentation of high-quality reinforcement (meat). Animals differed in terms of their food-procuring strategies, displaying "self-control," "ambivalence," or "impulsivity." Multineuron activity was recorded from the frontal cortex and hippocampus (field CA3). Cross-correlation analysis of interneuronal interactions within (local networks) and between (distributed networks) study structures showed that the numbers of interneuronal interactions in both local and distributed networks were maximal in animals with "self-control." On the background of systemic administration of the muscarinic cholinoreceptor blockers scopolamine and trihexyphenidyl, the numbers of interneuronal interactions decreased, while "common source" influences increased. This correlated with impairment of the reproduction of the selected strategy, primarily affecting the animals' self-controlled behavior. These results show that the "self-control" strategy is determined by the organization of local and distributed networks in the frontal cortex and hippocampus.

Social capital in a regional inter-hospital network among trauma centers (trauma network): results of a qualitative study in Germany.

PubMed

Loss, Julika; Weigl, Johannes; Ernstberger, Antonio; Nerlich, Michael; Koller, Michael; Curbach, Janina

2018-02-26

As inter-hospital alliances have become increasingly popular in the healthcare sector, it is important to understand the challenges and benefits that the interaction between representatives of different hospitals entail. A prominent example of inter-hospital alliances are certified 'trauma networks', which consist of 5-30 trauma departments in a given region. Trauma networks are designed to improve trauma care by providing a coordinated response to injury, and have developed across the USA and multiple European countries since the 1960s. Their members need to interact regularly, e.g. develop joint protocols for patient transfer, or discuss patient safety. Social capital is a concept focusing on the development and benefits of relations and interactions within a network. The aim of our study was to explore how social capital is generated and used in a regional German trauma network. In this qualitative study, we performed semi-standardized face-to-face interviews with 23 senior trauma surgeons (2013-14). They were the official representatives of 23 out of 26 member hospitals of the Trauma Network Eastern Bavaria. The interviews covered the structure and functioning of the network, climate and reciprocity within the network, the development of social identity, and different resources and benefits derived from the network (e.g. facilitation of interactions, advocacy, work satisfaction). Transcripts were coded using thematic content analysis. According to the interviews, the studied trauma network became a group of surgeons with substantial bonding social capital. The surgeons perceived that the network's culture of interaction was flat, and they identified with the network due to a climate of mutual respect. They felt that the inclusive leadership helped establish a norm of reciprocity. Among the interviewed surgeons, the gain of technical information was seen as less important than the exchange of information on political aspects. The perceived resources derived from this social capital were smoother interactions, a higher medical credibility, and joint advocacy securing certain privileges. Apart from addressing quality of care, a trauma network may, by way of strengthening social capital among its members, serve as a valuable resource for the participating surgeons. Some member hospitals could exploit the social capital for strategic benefits.

Weak Higher-Order Interactions in Macroscopic Functional Networks of the Resting Brain.

PubMed

Huang, Xuhui; Xu, Kaibin; Chu, Congying; Jiang, Tianzi; Yu, Shan

2017-10-25

Interactions among different brain regions are usually examined through functional connectivity (FC) analysis, which is exclusively based on measuring pairwise correlations in activities. However, interactions beyond the pairwise level, that is, higher-order interactions (HOIs), are vital in understanding the behavior of many complex systems. So far, whether HOIs exist among brain regions and how they can affect the brain's activities remains largely elusive. To address these issues, here, we analyzed blood oxygenation level-dependent (BOLD) signals recorded from six typical macroscopic functional networks of the brain in 100 human subjects (46 males and 54 females) during the resting state. Through examining the binarized BOLD signals, we found that HOIs within and across individual networks were both very weak regardless of the network size, topology, degree of spatial proximity, spatial scales, and whether the global signal was regressed. To investigate the potential mechanisms underlying the weak HOIs, we analyzed the dynamics of a network model and also found that HOIs were generally weak within a wide range of key parameters provided that the overall dynamic feature of the model was similar to the empirical data and it was operating close to a linear fluctuation regime. Our results suggest that weak HOI may be a general property of brain's macroscopic functional networks, which implies the dominance of pairwise interactions in shaping brain activities at such a scale and warrants the validity of widely used pairwise-based FC approaches. SIGNIFICANCE STATEMENT To explain how activities of different brain areas are coordinated through interactions is essential to revealing the mechanisms underlying various brain functions. Traditionally, such an interaction structure is commonly studied using pairwise-based functional network analyses. It is unclear whether the interactions beyond the pairwise level (higher-order interactions or HOIs) play any role in this process. Here, we show that HOIs are generally weak in macroscopic brain networks. We also suggest a possible dynamical mechanism that may underlie this phenomenon. These results provide plausible explanation for the effectiveness of widely used pairwise-based approaches in analyzing brain networks. More importantly, it reveals a previously unknown, simple organization of the brain's macroscopic functional systems. Copyright © 2017 the authors 0270-6474/17/3710481-17$15.00/0.

Understanding Classrooms through Social Network Analysis: A Primer for Social Network Analysis in Education Research

PubMed Central

Wiggins, Benjamin L.; Goodreau, Steven M.

2014-01-01

Social interactions between students are a major and underexplored part of undergraduate education. Understanding how learning relationships form in undergraduate classrooms, as well as the impacts these relationships have on learning outcomes, can inform educators in unique ways and improve educational reform. Social network analysis (SNA) provides the necessary tool kit for investigating questions involving relational data. We introduce basic concepts in SNA, along with methods for data collection, data processing, and data analysis, using a previously collected example study on an undergraduate biology classroom as a tutorial. We conduct descriptive analyses of the structure of the network of costudying relationships. We explore generative processes that create observed study networks between students and also test for an association between network position and success on exams. We also cover practical issues, such as the unique aspects of human subjects review for network studies. Our aims are to convince readers that using SNA in classroom environments allows rich and informative analyses to take place and to provide some initial tools for doing so, in the process inspiring future educational studies incorporating relational data. PMID:26086650

Signatures of Pleiotropy, Economy and Convergent Evolution in a Domain-Resolved Map of Human–Virus Protein–Protein Interaction Networks

PubMed Central

Garamszegi, Sara; Franzosa, Eric A.; Xia, Yu

2013-01-01

A central challenge in host-pathogen systems biology is the elucidation of general, systems-level principles that distinguish host-pathogen interactions from within-host interactions. Current analyses of host-pathogen and within-host protein-protein interaction networks are largely limited by their resolution, treating proteins as nodes and interactions as edges. Here, we construct a domain-resolved map of human-virus and within-human protein-protein interaction networks by annotating protein interactions with high-coverage, high-accuracy, domain-centric interaction mechanisms: (1) domain-domain interactions, in which a domain in one protein binds to a domain in a second protein, and (2) domain-motif interactions, in which a domain in one protein binds to a short, linear peptide motif in a second protein. Analysis of these domain-resolved networks reveals, for the first time, significant mechanistic differences between virus-human and within-human interactions at the resolution of single domains. While human proteins tend to compete with each other for domain binding sites by means of sequence similarity, viral proteins tend to compete with human proteins for domain binding sites in the absence of sequence similarity. Independent of their previously established preference for targeting human protein hubs, viral proteins also preferentially target human proteins containing linear motif-binding domains. Compared to human proteins, viral proteins participate in more domain-motif interactions, target more unique linear motif-binding domains per residue, and contain more unique linear motifs per residue. Together, these results suggest that viruses surmount genome size constraints by convergently evolving multiple short linear motifs in order to effectively mimic, hijack, and manipulate complex host processes for their survival. Our domain-resolved analyses reveal unique signatures of pleiotropy, economy, and convergent evolution in viral-host interactions that are otherwise hidden in the traditional binary network, highlighting the power and necessity of high-resolution approaches in host-pathogen systems biology. PMID:24339775

Signatures of pleiotropy, economy and convergent evolution in a domain-resolved map of human-virus protein-protein interaction networks.

PubMed

Garamszegi, Sara; Franzosa, Eric A; Xia, Yu

2013-01-01

A central challenge in host-pathogen systems biology is the elucidation of general, systems-level principles that distinguish host-pathogen interactions from within-host interactions. Current analyses of host-pathogen and within-host protein-protein interaction networks are largely limited by their resolution, treating proteins as nodes and interactions as edges. Here, we construct a domain-resolved map of human-virus and within-human protein-protein interaction networks by annotating protein interactions with high-coverage, high-accuracy, domain-centric interaction mechanisms: (1) domain-domain interactions, in which a domain in one protein binds to a domain in a second protein, and (2) domain-motif interactions, in which a domain in one protein binds to a short, linear peptide motif in a second protein. Analysis of these domain-resolved networks reveals, for the first time, significant mechanistic differences between virus-human and within-human interactions at the resolution of single domains. While human proteins tend to compete with each other for domain binding sites by means of sequence similarity, viral proteins tend to compete with human proteins for domain binding sites in the absence of sequence similarity. Independent of their previously established preference for targeting human protein hubs, viral proteins also preferentially target human proteins containing linear motif-binding domains. Compared to human proteins, viral proteins participate in more domain-motif interactions, target more unique linear motif-binding domains per residue, and contain more unique linear motifs per residue. Together, these results suggest that viruses surmount genome size constraints by convergently evolving multiple short linear motifs in order to effectively mimic, hijack, and manipulate complex host processes for their survival. Our domain-resolved analyses reveal unique signatures of pleiotropy, economy, and convergent evolution in viral-host interactions that are otherwise hidden in the traditional binary network, highlighting the power and necessity of high-resolution approaches in host-pathogen systems biology.

Functional Genomics Assistant (FUGA): a toolbox for the analysis of complex biological networks

PubMed Central

2011-01-01

Background Cellular constituents such as proteins, DNA, and RNA form a complex web of interactions that regulate biochemical homeostasis and determine the dynamic cellular response to external stimuli. It follows that detailed understanding of these patterns is critical for the assessment of fundamental processes in cell biology and pathology. Representation and analysis of cellular constituents through network principles is a promising and popular analytical avenue towards a deeper understanding of molecular mechanisms in a system-wide context. Findings We present Functional Genomics Assistant (FUGA) - an extensible and portable MATLAB toolbox for the inference of biological relationships, graph topology analysis, random network simulation, network clustering, and functional enrichment statistics. In contrast to conventional differential expression analysis of individual genes, FUGA offers a framework for the study of system-wide properties of biological networks and highlights putative molecular targets using concepts of systems biology. Conclusion FUGA offers a simple and customizable framework for network analysis in a variety of systems biology applications. It is freely available for individual or academic use at http://code.google.com/p/fuga. PMID:22035155

Description of a method to support public health information management: organizational network analysis

PubMed Central

Merrill, Jacqueline; Bakken, Suzanne; Rockoff, Maxine; Gebbie, Kristine; Carley, Kathleen

2007-01-01

In this case study we describe a method that has potential to provide systematic support for public health information management. Public health agencies depend on specialized information that travels throughout an organization via communication networks among employees. Interactions that occur within these networks are poorly understood and are generally unmanaged. We applied organizational network analysis, a method for studying communication networks, to assess the method’s utility to support decision making for public health managers, and to determine what links existed between information use and agency processes. Data on communication links among a health department’s staff was obtained via survey with a 93% response rate, and analyzed using Organizational Risk Analyzer (ORA) software. The findings described the structure of information flow in the department’s communication networks. The analysis succeeded in providing insights into organizational processes which informed public health managers’ strategies to address problems and to take advantage of network strengths. PMID:17098480

Challenges in network science: Applications to infrastructures, climate, social systems and economics

NASA Astrophysics Data System (ADS)

Havlin, S.; Kenett, D. Y.; Ben-Jacob, E.; Bunde, A.; Cohen, R.; Hermann, H.; Kantelhardt, J. W.; Kertész, J.; Kirkpatrick, S.; Kurths, J.; Portugali, J.; Solomon, S.

2012-11-01

Network theory has become one of the most visible theoretical frameworks that can be applied to the description, analysis, understanding, design and repair of multi-level complex systems. Complex networks occur everywhere, in man-made and human social systems, in organic and inorganic matter, from nano to macro scales, and in natural and anthropogenic structures. New applications are developed at an ever-increasing rate and the promise for future growth is high, since increasingly we interact with one another within these vital and complex environments. Despite all the great successes of this field, crucial aspects of multi-level complex systems have been largely ignored. Important challenges of network science are to take into account many of these missing realistic features such as strong coupling between networks (networks are not isolated), the dynamics of networks (networks are not static), interrelationships between structure, dynamics and function of networks, interdependencies in given networks (and other classes of links, including different signs of interactions), and spatial properties (including geographical aspects) of networks. This aim of this paper is to introduce and discuss the challenges that future network science needs to address, and how different disciplines will be accordingly affected.

A network meta-analysis on the effects of information technology application on preoperative knowledge of patients.

PubMed

Lai, Yi-Horng

2015-01-01

The application of information technology in health education plan in Taiwan has existed for a long time. The purpose of this study is to explore the relationship between information technology application in health education and patients' preoperative knowledge by synthesizing existing researches that compare the effectiveness of information technology application and traditional instruction in the health education plan. In spite of claims regarding the potential benefits of using information technology in health education plan, results of previous researches were conflicting. This study is carried out to examine the effectiveness of information technology by using network meta-analysis, which is a statistical analysis of separate but similar studies in order to test the pooled data for statistical significance. Information technology application in health education discussed in this study include interactive technology therapy (person-computer), group interactive technology therapy (person-person), multimedia technology therapy and video therapy. The result has shown that group interactive technology therapy is the most effective, followed by interactive technology therapy. And these four therapies of information technology are all superior to the traditional health education plan (leaflet therapy).

Exploratory Study on the Patterns of Online Interaction and Knowledge Co-Construction in Project-Based Learning

ERIC Educational Resources Information Center

Heo, Heeok; Lim, Kyu Yon; Kim, Youngsoo

2010-01-01

This study aims to investigate the patterns and the quality of online interaction during project-based learning (PjBL) on both micro and macro levels. To achieve this purpose, PjBL was implemented with online group activities in an undergraduate course. Social network analysis (SNA) and content analysis were employed to analyze online interaction…

Levels and Patterns of Participation and Social Interaction in an Online Learning Community for Learning to Teach

ERIC Educational Resources Information Center

Tsai, I-Chun

2011-01-01

This study investigates how pre-service and in-service teachers participate in an online community for learning to teach. Members' levels and patterns of participation and social interaction were examined via social network analysis of activity logs and content analysis of interviews. The results of the analyses show that (a) members' levels and…

Fuzzy Entropy Method for Quantifying Supply Chain Networks Complexity

NASA Astrophysics Data System (ADS)

Zhang, Jihui; Xu, Junqin

Supply chain is a special kind of complex network. Its complexity and uncertainty makes it very difficult to control and manage. Supply chains are faced with a rising complexity of products, structures, and processes. Because of the strong link between a supply chain’s complexity and its efficiency the supply chain complexity management becomes a major challenge of today’s business management. The aim of this paper is to quantify the complexity and organization level of an industrial network working towards the development of a ‘Supply Chain Network Analysis’ (SCNA). By measuring flows of goods and interaction costs between different sectors of activity within the supply chain borders, a network of flows is built and successively investigated by network analysis. The result of this study shows that our approach can provide an interesting conceptual perspective in which the modern supply network can be framed, and that network analysis can handle these issues in practice.

Reducing neural network training time with parallel processing

NASA Technical Reports Server (NTRS)

Rogers, James L., Jr.; Lamarsh, William J., II

1995-01-01

Obtaining optimal solutions for engineering design problems is often expensive because the process typically requires numerous iterations involving analysis and optimization programs. Previous research has shown that a near optimum solution can be obtained in less time by simulating a slow, expensive analysis with a fast, inexpensive neural network. A new approach has been developed to further reduce this time. This approach decomposes a large neural network into many smaller neural networks that can be trained in parallel. Guidelines are developed to avoid some of the pitfalls when training smaller neural networks in parallel. These guidelines allow the engineer: to determine the number of nodes on the hidden layer of the smaller neural networks; to choose the initial training weights; and to select a network configuration that will capture the interactions among the smaller neural networks. This paper presents results describing how these guidelines are developed.

Bayesian network prior: network analysis of biological data using external knowledge

PubMed Central

Isci, Senol; Dogan, Haluk; Ozturk, Cengizhan; Otu, Hasan H.

2014-01-01

Motivation: Reverse engineering GI networks from experimental data is a challenging task due to the complex nature of the networks and the noise inherent in the data. One way to overcome these hurdles would be incorporating the vast amounts of external biological knowledge when building interaction networks. We propose a framework where GI networks are learned from experimental data using Bayesian networks (BNs) and the incorporation of external knowledge is also done via a BN that we call Bayesian Network Prior (BNP). BNP depicts the relation between various evidence types that contribute to the event ‘gene interaction’ and is used to calculate the probability of a candidate graph (G) in the structure learning process. Results: Our simulation results on synthetic, simulated and real biological data show that the proposed approach can identify the underlying interaction network with high accuracy even when the prior information is distorted and outperforms existing methods. Availability: Accompanying BNP software package is freely available for academic use at http://bioe.bilgi.edu.tr/BNP. Contact: hasan.otu@bilgi.edu.tr Supplementary Information: Supplementary data are available at Bioinformatics online. PMID:24215027

Unravelling networks in local public health policymaking in three European countries - a systems analysis.

PubMed

Spitters, Hilde P E M; Lau, Cathrine J; Sandu, Petru; Quanjel, Marcel; Dulf, Diana; Glümer, Charlotte; van Oers, Hans A M; van de Goor, Ien A M

2017-02-03

Facilitating and enhancing interaction between stakeholders involved in the policymaking process to stimulate collaboration and use of evidence, is important to foster the development of effective Health Enhancing Physical Activity (HEPA) policies. Performing an analysis of real-world policymaking processes will help reveal the complexity of a network of stakeholders. Therefore, the main objectives were to unravel the stakeholder network in the policy process by conducting three systems analyses, and to increase insight into the similarities and differences in the policy processes of these European country cases. A systems analysis of the local HEPA policymaking process was performed in three European countries involved in the 'REsearch into POlicy to enhance Physical Activity' (REPOPA) project, resulting in three schematic models showing the main stakeholders and their relationships. The models were used to compare the systems, focusing on implications with respect to collaboration and use of evidence in local HEPA policymaking. Policy documents and relevant webpages were examined and main stakeholders were interviewed. The systems analysis in each country identified the main stakeholders involved and their position and relations in the policymaking process. The Netherlands and Denmark were the most similar and both differed most from Romania, especially at the level of accountability of the local public authorities for local HEPA policymaking. The categories of driving forces underlying the relations between stakeholders were formal relations, informal interaction and knowledge exchange. A systems analysis providing detailed descriptions of positions and relations in the stakeholder network in local level HEPA policymaking is rather unique in this area. The analyses are useful when a need arises for increased interaction, collaboration and use of knowledge between stakeholders in the local HEPA network, as they provide an overview of the stakeholders involved and their mutual relations. This information can be an important starting point to enhance the uptake of evidence and build more effective public health policies.

Identification and functional analysis of risk-related microRNAs for the prognosis of patients with bladder urothelial carcinoma.

PubMed

Gao, Ji; Li, Hongyan; Liu, Lei; Song, Lide; Lv, Yanting; Han, Yuping

2017-12-01

The aim of the present study was to investigate risk-related microRNAs (miRs) for bladder urothelial carcinoma (BUC) prognosis. Clinical and microRNA expression data downloaded from the Cancer Genome Atlas were utilized for survival analysis. Risk factor estimation was performed using Cox's proportional regression analysis. A microRNA-regulated target gene network was constructed and presented using Cytoscape. In addition, the Database for Annotation, Visualization and Integrated Discovery was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment, followed by protein-protein interaction (PPI) network analysis. Finally, the K-clique method was applied to analyze sub-pathways. A total of 16 significant microRNAs, including hsa-miR-3622a and hsa-miR-29a, were identified (P<0.05). Following Cox's proportional regression analysis, hsa-miR-29a was screened as a prognostic marker of BUC risk (P=0.0449). A regulation network of hsa-miR-29a comprising 417 target genes was constructed. These target genes were primarily enriched in GO terms, including collagen fibril organization, extracellular matrix (ECM) organization and pathways, such as focal adhesion (P<0.05). A PPI network including 197 genes and 510 interactions, was constructed. The top 21 genes in the network module were enriched in GO terms, including collagen fibril organization and pathways, such as ECM receptor interaction (P<0.05). Finally, 4 sub-pathways of cysteine and methionine metabolism, including paths 00270_4, 00270_1, 00270_2 and 00270_5, were obtained (P<0.01) and identified to be enriched through DNA (cytosine-5)-methyltransferase ( DNMT)3A, DNMT3B , methionine adenosyltransferase 2α ( MAT2A ) and spermine synthase ( SMS ). The identified microRNAs, particularly hsa-miR-29a and its 4 associated target genes DNMT3A, DNMT3B, MAT2A and SMS , may participate in the prognostic risk mechanism of BUC.

Atlas of Cancer Signalling Network: a systems biology resource for integrative analysis of cancer data with Google Maps

PubMed Central

Kuperstein, I; Bonnet, E; Nguyen, H-A; Cohen, D; Viara, E; Grieco, L; Fourquet, S; Calzone, L; Russo, C; Kondratova, M; Dutreix, M; Barillot, E; Zinovyev, A

2015-01-01

Cancerogenesis is driven by mutations leading to aberrant functioning of a complex network of molecular interactions and simultaneously affecting multiple cellular functions. Therefore, the successful application of bioinformatics and systems biology methods for analysis of high-throughput data in cancer research heavily depends on availability of global and detailed reconstructions of signalling networks amenable for computational analysis. We present here the Atlas of Cancer Signalling Network (ACSN), an interactive and comprehensive map of molecular mechanisms implicated in cancer. The resource includes tools for map navigation, visualization and analysis of molecular data in the context of signalling network maps. Constructing and updating ACSN involves careful manual curation of molecular biology literature and participation of experts in the corresponding fields. The cancer-oriented content of ACSN is completely original and covers major mechanisms involved in cancer progression, including DNA repair, cell survival, apoptosis, cell cycle, EMT and cell motility. Cell signalling mechanisms are depicted in detail, together creating a seamless ‘geographic-like' map of molecular interactions frequently deregulated in cancer. The map is browsable using NaviCell web interface using the Google Maps engine and semantic zooming principle. The associated web-blog provides a forum for commenting and curating the ACSN content. ACSN allows uploading heterogeneous omics data from users on top of the maps for visualization and performing functional analyses. We suggest several scenarios for ACSN application in cancer research, particularly for visualizing high-throughput data, starting from small interfering RNA-based screening results or mutation frequencies to innovative ways of exploring transcriptomes and phosphoproteomes. Integration and analysis of these data in the context of ACSN may help interpret their biological significance and formulate mechanistic hypotheses. ACSN may also support patient stratification, prediction of treatment response and resistance to cancer drugs, as well as design of novel treatment strategies. PMID:26192618

Bayesian switching factor analysis for estimating time-varying functional connectivity in fMRI.

PubMed

Taghia, Jalil; Ryali, Srikanth; Chen, Tianwen; Supekar, Kaustubh; Cai, Weidong; Menon, Vinod

2017-07-15

There is growing interest in understanding the dynamical properties of functional interactions between distributed brain regions. However, robust estimation of temporal dynamics from functional magnetic resonance imaging (fMRI) data remains challenging due to limitations in extant multivariate methods for modeling time-varying functional interactions between multiple brain areas. Here, we develop a Bayesian generative model for fMRI time-series within the framework of hidden Markov models (HMMs). The model is a dynamic variant of the static factor analysis model (Ghahramani and Beal, 2000). We refer to this model as Bayesian switching factor analysis (BSFA) as it integrates factor analysis into a generative HMM in a unified Bayesian framework. In BSFA, brain dynamic functional networks are represented by latent states which are learnt from the data. Crucially, BSFA is a generative model which estimates the temporal evolution of brain states and transition probabilities between states as a function of time. An attractive feature of BSFA is the automatic determination of the number of latent states via Bayesian model selection arising from penalization of excessively complex models. Key features of BSFA are validated using extensive simulations on carefully designed synthetic data. We further validate BSFA using fingerprint analysis of multisession resting-state fMRI data from the Human Connectome Project (HCP). Our results show that modeling temporal dependencies in the generative model of BSFA results in improved fingerprinting of individual participants. Finally, we apply BSFA to elucidate the dynamic functional organization of the salience, central-executive, and default mode networks-three core neurocognitive systems with central role in cognitive and affective information processing (Menon, 2011). Across two HCP sessions, we demonstrate a high level of dynamic interactions between these networks and determine that the salience network has the highest temporal flexibility among the three networks. Our proposed methods provide a novel and powerful generative model for investigating dynamic brain connectivity. Copyright © 2017 Elsevier Inc. All rights reserved.

Social Networking Analysis: One of the First Steps in Net-Centric Operations

DTIC Science & Technology

2005-01-01

came to form part of current management thought and is transforming the ways of thinking about social relationships in management and leadership in...about social relationships and leadership in government and commercial organizations. This paper will highlight how network analysis has become...relevant to management studies, how it is transforming how we study social relationships , how it can be used to understand how actors interact (especially

Identification of Linkages between EDCs in Personal Care Products and Breast Cancer through Data Integration Combined with Gene Network Analysis.

PubMed

Jeong, Hyeri; Kim, Jongwoon; Kim, Youngjun

2017-09-30

Approximately 1000 chemicals have been reported to possibly have endocrine disrupting effects, some of which are used in consumer products, such as personal care products (PCPs) and cosmetics. We conducted data integration combined with gene network analysis to: (i) identify causal molecular mechanisms between endocrine disrupting chemicals (EDCs) used in PCPs and breast cancer; and (ii) screen candidate EDCs associated with breast cancer. Among EDCs used in PCPs, four EDCs having correlation with breast cancer were selected, and we curated 27 common interacting genes between those EDCs and breast cancer to perform the gene network analysis. Based on the gene network analysis, ESR1, TP53, NCOA1, AKT1, and BCL6 were found to be key genes to demonstrate the molecular mechanisms of EDCs in the development of breast cancer. Using GeneMANIA, we additionally predicted 20 genes which could interact with the 27 common genes. In total, 47 genes combining the common and predicted genes were functionally grouped with the gene ontology and KEGG pathway terms. With those genes, we finally screened candidate EDCs for their potential to increase breast cancer risk. This study highlights that our approach can provide insights to understand mechanisms of breast cancer and identify potential EDCs which are in association with breast cancer.

Dynamics and causalities of atmospheric and oceanic data identified by complex networks and Granger causality analysis

NASA Astrophysics Data System (ADS)

Charakopoulos, A. K.; Katsouli, G. A.; Karakasidis, T. E.

2018-04-01

Understanding the underlying processes and extracting detailed characteristics of spatiotemporal dynamics of ocean and atmosphere as well as their interaction is of significant interest and has not been well thoroughly established. The purpose of this study was to examine the performance of two main additional methodologies for the identification of spatiotemporal underlying dynamic characteristics and patterns among atmospheric and oceanic variables from Seawatch buoys from Aegean and Ionian Sea, provided by the Hellenic Center for Marine Research (HCMR). The first approach involves the estimation of cross correlation analysis in an attempt to investigate time-lagged relationships, and further in order to identify the direction of interactions between the variables we performed the Granger causality method. According to the second approach the time series are converted into complex networks and then the main topological network properties such as degree distribution, average path length, diameter, modularity and clustering coefficient are evaluated. Our results show that the proposed analysis of complex network analysis of time series can lead to the extraction of hidden spatiotemporal characteristics. Also our findings indicate high level of positive and negative correlations and causalities among variables, both from the same buoy and also between buoys from different stations, which cannot be determined from the use of simple statistical measures.

The effect of habitat modification on plant-pollinator network

NASA Astrophysics Data System (ADS)

Aminatun, Tien; Putra, Nugroho Susetya

2017-08-01

The research aimed to determine; (1) the mutualism interaction pattern of plant-pollinator on several habitat modifications; and (2) the habitat modification which showed the most stable pattern of interaction. The study was conducted in one planting season with 20 plots which each plot had 2x2 m2 width and 2 m spacing among plots, and each plot was planted with the same variety of tomato plants, i.e. "intan". Nitrogen manipulation treatment was conducted with four kinds of fertilizers, i.e. NPK (code PU), compost (code PKM), vermicompost (code PC), and manure (code PK). Each treatment had 5 plot replications. We observed the growth of tomato plants, weed and arthropod populationstwo weekly while pollinator visitation twice a week during tomato plant flowering with counting population and visitation frequence of each pollinator on each sample of tomato plants. The nectar of tomato plant flower of each treatment was tested in laboratory to see its reducing sugar and sucrose. Oganic matter and nitrogen of the soil samples of each treatment were tested in laboratory in the beginning and the end of this research. We analized the plant-pollinator network with bipartite program in R-statistics, and the abiotic and other biotic factors with descriptive analysis. The results of the research were; (1) the mutualism interaction pattern of plant-pollinator network of four treatments were varied, and (2) The pattern of plant-pollinator network of NPK fertilizer treatment showed the more stable interaction based on analysis of interaction evenness, Shannon diversity, frequency and longevity of pollinator visitation.

The effect of individual variation on the structure and function of interaction networks in harvester ants

PubMed Central

Pinter-Wollman, Noa; Wollman, Roy; Guetz, Adam; Holmes, Susan; Gordon, Deborah M.

2011-01-01

Social insects exhibit coordinated behaviour without central control. Local interactions among individuals determine their behaviour and regulate the activity of the colony. Harvester ants are recruited for outside work, using networks of brief antennal contacts, in the nest chamber closest to the nest exit: the entrance chamber. Here, we combine empirical observations, image analysis and computer simulations to investigate the structure and function of the interaction network in the entrance chamber. Ant interactions were distributed heterogeneously in the chamber, with an interaction hot-spot at the entrance leading further into the nest. The distribution of the total interactions per ant followed a right-skewed distribution, indicating the presence of highly connected individuals. Numbers of ant encounters observed positively correlated with the duration of observation. Individuals varied in interaction frequency, even after accounting for the duration of observation. An ant's interaction frequency was explained by its path shape and location within the entrance chamber. Computer simulations demonstrate that variation among individuals in connectivity accelerates information flow to an extent equivalent to an increase in the total number of interactions. Individual variation in connectivity, arising from variation among ants in location and spatial behaviour, creates interaction centres, which may expedite information flow. PMID:21490001

Flow interaction based propagation model and bursty influence behavior analysis of Internet flows

NASA Astrophysics Data System (ADS)

Wu, Xiao-Yu; Gu, Ren-Tao; Ji, Yue-Feng

2016-11-01

QoS (quality of service) fluctuations caused by Internet bursty flows influence the user experience in the Internet, such as the increment of packet loss and transmission time. In this paper, we establish a mathematical model to study the influence propagation behavior of the bursty flow, which is helpful for developing a deep understanding of the network dynamics in the Internet complex system. To intuitively reflect the propagation process, a data flow interaction network with a hierarchical structure is constructed, where the neighbor order is proposed to indicate the neighborhood relationship between the bursty flow and other flows. The influence spreads from the bursty flow to each order of neighbors through flow interactions. As the influence spreads, the bursty flow has negative effects on the odd order neighbors and positive effects on the even order neighbors. The influence intensity of bursty flow decreases sharply between two adjacent orders and the decreasing degree can reach up to dozens of times in the experimental simulation. Moreover, the influence intensity increases significantly when network congestion situation becomes serious, especially for the 1st order neighbors. Network structural factors are considered to make a further study. Simulation results show that the physical network scale expansion can reduce the influence intensity of bursty flow by decreasing the flow distribution density. Furthermore, with the same network scale, the influence intensity in WS small-world networks is 38.18% and 18.40% lower than that in ER random networks and BA scale-free networks, respectively, due to a lower interaction probability between flows. These results indicate that the macro-structural changes such as network scales and styles will affect the inner propagation behaviors of the bursty flow.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Granger, Brian R.; Chang, Yi -Chien; Wang, Yan

Here, the complexity of metabolic networks in microbial communities poses an unresolved visualization and interpretation challenge. We address this challenge in the newly expanded version of a software tool for the analysis of biological networks, VisANT 5.0. We focus in particular on facilitating the visual exploration of metabolic interaction between microbes in a community, e.g. as predicted by COMETS (Computation of Microbial Ecosystems in Time and Space), a dynamic stoichiometric modeling framework. Using VisANT's unique meta-graph implementation, we show how one can use VisANT 5.0 to explore different time-dependent ecosystem-level metabolic networks. In particular, we analyze the metabolic interaction networkmore » between two bacteria previously shown to display an obligate cross-feeding interdependency. In addition, we illustrate how a putative minimal gut microbiome community could be represented in our framework, making it possible to highlight interactions across multiple coexisting species. We envisage that the "symbiotic layout" of VisANT can be employed as a general tool for the analysis of metabolism in complex microbial communities as well as heterogeneous human tissues.« less

HTS-Net: An integrated regulome-interactome approach for establishing network regulation models in high-throughput screenings

PubMed Central

Rioualen, Claire; Da Costa, Quentin; Chetrit, Bernard; Charafe-Jauffret, Emmanuelle; Ginestier, Christophe

2017-01-01

High-throughput RNAi screenings (HTS) allow quantifying the impact of the deletion of each gene in any particular function, from virus-host interactions to cell differentiation. However, there has been less development for functional analysis tools dedicated to RNAi analyses. HTS-Net, a network-based analysis program, was developed to identify gene regulatory modules impacted in high-throughput screenings, by integrating transcription factors-target genes interaction data (regulome) and protein-protein interaction networks (interactome) on top of screening z-scores. HTS-Net produces exhaustive HTML reports for results navigation and exploration. HTS-Net is a new pipeline for RNA interference screening analyses that proves better performance than simple gene rankings by z-scores, by re-prioritizing genes and replacing them in their biological context, as shown by the three studies that we reanalyzed. Formatted input data for the three studied datasets, source code and web site for testing the system are available from the companion web site at http://htsnet.marseille.inserm.fr/. We also compared our program with existing algorithms (CARD and hotnet2). PMID:28949986

The paradox of caffeine-zolpidem interaction: a network analysis.

PubMed

Myslobodsky, Michael

2009-10-01

A widely prescribed and potent short-acting hypnotic, zolpidem has become the mainstay for the treatment of middle-of-the-night sleeplessness. It is expected to be antagonized by caffeine. Paradoxically, in some cases caffeine appears to slightly enhance zolpidem sedation. The pharmacokinetic and pharmacodynamic nature of this odd effect remains unexplored. The purpose of this study is to reproduce a hypothetical molecular network recruited by caffeine when co-administered with zolpidem using Ingenuity Pathway Analysis. Thus generated, network drew attention to several possible contributors to caffeine sedation, such as tachykinin precursor 1, cannabinoid, and GABA receptors. The present overview is centered on the possibility that caffeine potentiation of zolpidem sedation does not involve a centralized interaction of specific neurotransmitters, but rather is contributed by its antioxidant capacity. It is proposed that by modifying the cellular redox state, caffeine ultimately reduces the pool of reactive oxygen species, thereby increasing the bioavailability of endogenous melatonin for interaction with zolpidem. This side effect of caffeine encourages further studies of multiple antioxidants as an attractive way to potentially increasing somnolence.

Unraveling novel broad-spectrum antibacterial targets in food and waterborne pathogens using comparative genomics and protein interaction network analysis.

PubMed

Jadhav, Ankush; Shanmugham, Buvaneswari; Rajendiran, Anjana; Pan, Archana

2014-10-01

Food and waterborne diseases are a growing concern in terms of human morbidity and mortality worldwide, even in the 21st century, emphasizing the need for new therapeutic interventions for these diseases. The current study aims at prioritizing broad-spectrum antibacterial targets, present in multiple food and waterborne bacterial pathogens, through a comparative genomics strategy coupled with a protein interaction network analysis. The pathways unique and common to all the pathogens under study (viz., methane metabolism, d-alanine metabolism, peptidoglycan biosynthesis, bacterial secretion system, two-component system, C5-branched dibasic acid metabolism), identified by comparative metabolic pathway analysis, were considered for the analysis. The proteins/enzymes involved in these pathways were prioritized following host non-homology analysis, essentiality analysis, gut flora non-homology analysis and protein interaction network analysis. The analyses revealed a set of promising broad-spectrum antibacterial targets, present in multiple food and waterborne pathogens, which are essential for bacterial survival, non-homologous to host and gut flora, and functionally important in the metabolic network. The identified broad-spectrum candidates, namely, integral membrane protein/virulence factor (MviN), preprotein translocase subunits SecB and SecG, carbon storage regulator (CsrA), and nitrogen regulatory protein P-II 1 (GlnB), contributed by the peptidoglycan pathway, bacterial secretion systems and two-component systems, were also found to be present in a wide range of other disease-causing bacteria. Cytoplasmic proteins SecG, CsrA and GlnB were considered as drug targets, while membrane proteins MviN and SecB were classified as vaccine targets. The identified broad-spectrum targets can aid in the design and development of antibacterial agents not only against food and waterborne pathogens but also against other pathogens. Copyright © 2014 Elsevier B.V. All rights reserved.

Analysis Of Using Firewall And Single Honeypot In Training Attack On Wireless Network

NASA Astrophysics Data System (ADS)

Mohd. Diansyah, Tengku.; Faisal, Ilham; Perdana, Adidtya; Octaviani Sembiring, Boni; Hidayati Sinaga, Tantri

2017-12-01

Security issues become one of the important aspects of a network, especially a network security on the server. These problems underlie the need to build a system that can detect threats from parties who do not have access rights (hackers) that are by building a security system honeypot. A Honeypot is a diversion of intruders' attention, in order for intruders to think that it has managed to break down and retrieve data from a network, when in fact the data is not important and the location is isolated. A way to trap or deny unauthorized use of effort in an information system. One type of honeypot is honeyd. Honeyd is a low interaction honeypot that has a smaller risk compared to high interaction types because the interaction with the honeypot does not directly involve the real system. The purpose of the implementation of honeypot and firewall, firewall is used on Mikrotik. Can be used as an administrative tool to view reports of Honeyd generated activity and administrators can also view reports that are stored in the logs in order to assist in determining network security policies.

Emerging Frontiers of Neuroengineering: A Network Science of Brain Connectivity

PubMed Central

Bassett, Danielle S.; Khambhati, Ankit N.; Grafton, Scott T.

2018-01-01

Neuroengineering is faced with unique challenges in repairing or replacing complex neural systems that are composed of many interacting parts. These interactions form intricate patterns over large spatiotemporal scales and produce emergent behaviors that are difficult to predict from individual elements. Network science provides a particularly appropriate framework in which to study and intervene in such systems by treating neural elements (cells, volumes) as nodes in a graph and neural interactions (synapses, white matter tracts) as edges in that graph. Here, we review the emerging discipline of network neuroscience, which uses and develops tools from graph theory to better understand and manipulate neural systems from micro- to macroscales. We present examples of how human brain imaging data are being modeled with network analysis and underscore potential pitfalls. We then highlight current computational and theoretical frontiers and emphasize their utility in informing diagnosis and monitoring, brain–machine interfaces, and brain stimulation. A flexible and rapidly evolving enterprise, network neuroscience provides a set of powerful approaches and fundamental insights that are critical for the neuroengineer’s tool kit. PMID:28375650

An association network analysis among microeukaryotes and bacterioplankton reveals algal bloom dynamics.

PubMed

Tan, Shangjin; Zhou, Jin; Zhu, Xiaoshan; Yu, Shichen; Zhan, Wugen; Wang, Bo; Cai, Zhonghua

2015-02-01

Algal blooms are a worldwide phenomenon and the biological interactions that underlie their regulation are only just beginning to be understood. It is established that algal microorganisms associate with many other ubiquitous, oceanic organisms, but the interactions that lead to the dynamics of bloom formation are currently unknown. To address this gap, we used network approaches to investigate the association patterns among microeukaryotes and bacterioplankton in response to a natural Scrippsiella trochoidea bloom. This is the first study to apply network approaches to bloom dynamics. To this end, terminal restriction fragment (T-RF) length polymorphism analysis showed dramatic changes in community compositions of microeukaryotes and bacterioplankton over the blooming period. A variance ratio test revealed significant positive overall associations both within and between microeukaryotic and bacterioplankton communities. An association network generated from significant correlations between T-RFs revealed that S. trochoidea had few connections to other microeukaryotes and bacterioplankton and was placed on the edge. This lack of connectivity allowed for the S. trochoidea sub-network to break off from the overall network. These results allowed us to propose a conceptual model for explaining how changes in microbial associations regulate the dynamics of an algal bloom. In addition, key T-RFs were screened by principal components analysis, correlation coefficients, and network analysis. Dominant T-RFs were then identified through 18S and 16S rRNA gene clone libraries. Results showed that microeukaryotes clustered predominantly with Dinophyceae and Perkinsea while the majority of bacterioplankton identified were Alphaproteobacteria, Gammaproteobacteria, and Bacteroidetes. The ecologi-cal roles of both were discussed in the context of these findings. © 2014 Phycological Society of America.

TP53 mutations, expression and interaction networks in human cancers

PubMed Central

Wang, Xiaosheng; Sun, Qingrong

2017-01-01

Although the associations of p53 dysfunction, p53 interaction networks and oncogenesis have been widely explored, a systematic analysis of TP53 mutations and its related interaction networks in various types of human cancers is lacking. Our study explored the associations of TP53 mutations, gene expression, clinical outcomes, and TP53 interaction networks across 33 cancer types using data from The Cancer Genome Atlas (TCGA). We show that TP53 is the most frequently mutated gene in a number of cancers, and its mutations appear to be early events in cancer initiation. We identified genes potentially repressed by p53, and genes whose expression correlates significantly with TP53 expression. These gene products may be especially important nodes in p53 interaction networks in human cancers. This study shows that while TP53-truncating mutations often result in decreased TP53 expression, other non-truncating TP53 mutations result in increased TP53 expression in some cancers. Survival analyses in a number of cancers show that patients with TP53 mutations are more likely to have worse prognoses than TP53-wildtype patients, and that elevated TP53 expression often leads to poor clinical outcomes. We identified a set of candidate synthetic lethal (SL) genes for TP53, and validated some of these SL interactions using data from the Cancer Cell Line Project. These predicted SL genes are promising candidates for experimental validation and the development of personalized therapeutics for patients with TP53-mutated cancers. PMID:27880943

TP53 mutations, expression and interaction networks in human cancers.

PubMed

Wang, Xiaosheng; Sun, Qingrong

2017-01-03

Although the associations of p53 dysfunction, p53 interaction networks and oncogenesis have been widely explored, a systematic analysis of TP53 mutations and its related interaction networks in various types of human cancers is lacking. Our study explored the associations of TP53 mutations, gene expression, clinical outcomes, and TP53 interaction networks across 33 cancer types using data from The Cancer Genome Atlas (TCGA). We show that TP53 is the most frequently mutated gene in a number of cancers, and its mutations appear to be early events in cancer initiation. We identified genes potentially repressed by p53, and genes whose expression correlates significantly with TP53 expression. These gene products may be especially important nodes in p53 interaction networks in human cancers. This study shows that while TP53-truncating mutations often result in decreased TP53 expression, other non-truncating TP53 mutations result in increased TP53 expression in some cancers. Survival analyses in a number of cancers show that patients with TP53 mutations are more likely to have worse prognoses than TP53-wildtype patients, and that elevated TP53 expression often leads to poor clinical outcomes. We identified a set of candidate synthetic lethal (SL) genes for TP53, and validated some of these SL interactions using data from the Cancer Cell Line Project. These predicted SL genes are promising candidates for experimental validation and the development of personalized therapeutics for patients with TP53-mutated cancers.

Weighted and directed interactions in evolving large-scale epileptic brain networks

NASA Astrophysics Data System (ADS)

Dickten, Henning; Porz, Stephan; Elger, Christian E.; Lehnertz, Klaus

2016-10-01

Epilepsy can be regarded as a network phenomenon with functionally and/or structurally aberrant connections in the brain. Over the past years, concepts and methods from network theory substantially contributed to improve the characterization of structure and function of these epileptic networks and thus to advance understanding of the dynamical disease epilepsy. We extend this promising line of research and assess—with high spatial and temporal resolution and using complementary analysis approaches that capture different characteristics of the complex dynamics—both strength and direction of interactions in evolving large-scale epileptic brain networks of 35 patients that suffered from drug-resistant focal seizures with different anatomical onset locations. Despite this heterogeneity, we find that even during the seizure-free interval the seizure onset zone is a brain region that, when averaged over time, exerts strongest directed influences over other brain regions being part of a large-scale network. This crucial role, however, manifested by averaging on the population-sample level only - in more than one third of patients, strongest directed interactions can be observed between brain regions far off the seizure onset zone. This may guide new developments for individualized diagnosis, treatment and control.

Global Alignment of Pairwise Protein Interaction Networks for Maximal Common Conserved Patterns

DOE PAGES

Tian, Wenhong; Samatova, Nagiza F.

2013-01-01

A number of tools for the alignment of protein-protein interaction (PPI) networks have laid the foundation for PPI network analysis. Most of alignment tools focus on finding conserved interaction regions across the PPI networks through either local or global mapping of similar sequences. Researchers are still trying to improve the speed, scalability, and accuracy of network alignment. In view of this, we introduce a connected-components based fast algorithm, HopeMap, for network alignment. Observing that the size of true orthologs across species is small comparing to the total number of proteins in all species, we take a different approach based onmore » a precompiled list of homologs identified by KO terms. Applying this approach to S. cerevisiae (yeast) and D. melanogaster (fly), E. coli K12 and S. typhimurium , E. coli K12 and C. crescenttus , we analyze all clusters identified in the alignment. The results are evaluated through up-to-date known gene annotations, gene ontology (GO), and KEGG ortholog groups (KO). Comparing to existing tools, our approach is fast with linear computational cost, highly accurate in terms of KO and GO terms specificity and sensitivity, and can be extended to multiple alignments easily.« less

A Novel Framework for the Comparative Analysis of Biological Networks

PubMed Central

Pache, Roland A.; Aloy, Patrick

2012-01-01

Genome sequencing projects provide nearly complete lists of the individual components present in an organism, but reveal little about how they work together. Follow-up initiatives have deciphered thousands of dynamic and context-dependent interrelationships between gene products that need to be analyzed with novel bioinformatics approaches able to capture their complex emerging properties. Here, we present a novel framework for the alignment and comparative analysis of biological networks of arbitrary topology. Our strategy includes the prediction of likely conserved interactions, based on evolutionary distances, to counter the high number of missing interactions in the current interactome networks, and a fast assessment of the statistical significance of individual alignment solutions, which vastly increases its performance with respect to existing tools. Finally, we illustrate the biological significance of the results through the identification of novel complex components and potential cases of cross-talk between pathways and alternative signaling routes. PMID:22363585

Duality between Time Series and Networks

PubMed Central

Campanharo, Andriana S. L. O.; Sirer, M. Irmak; Malmgren, R. Dean; Ramos, Fernando M.; Amaral, Luís A. Nunes.

2011-01-01

Studying the interaction between a system's components and the temporal evolution of the system are two common ways to uncover and characterize its internal workings. Recently, several maps from a time series to a network have been proposed with the intent of using network metrics to characterize time series. Although these maps demonstrate that different time series result in networks with distinct topological properties, it remains unclear how these topological properties relate to the original time series. Here, we propose a map from a time series to a network with an approximate inverse operation, making it possible to use network statistics to characterize time series and time series statistics to characterize networks. As a proof of concept, we generate an ensemble of time series ranging from periodic to random and confirm that application of the proposed map retains much of the information encoded in the original time series (or networks) after application of the map (or its inverse). Our results suggest that network analysis can be used to distinguish different dynamic regimes in time series and, perhaps more importantly, time series analysis can provide a powerful set of tools that augment the traditional network analysis toolkit to quantify networks in new and useful ways. PMID:21858093

Visualizing weighted networks: a performance comparison of adjacency matrices versus node-link diagrams

NASA Astrophysics Data System (ADS)

McIntire, John P.; Osesina, O. Isaac; Bartley, Cecilia; Tudoreanu, M. Eduard; Havig, Paul R.; Geiselman, Eric E.

2012-06-01

Ensuring the proper and effective ways to visualize network data is important for many areas of academia, applied sciences, the military, and the public. Fields such as social network analysis, genetics, biochemistry, intelligence, cybersecurity, neural network modeling, transit systems, communications, etc. often deal with large, complex network datasets that can be difficult to interact with, study, and use. There have been surprisingly few human factors performance studies on the relative effectiveness of different graph drawings or network diagram techniques to convey information to a viewer. This is particularly true for weighted networks which include the strength of connections between nodes, not just information about which nodes are linked to other nodes. We describe a human factors study in which participants performed four separate network analysis tasks (finding a direct link between given nodes, finding an interconnected node between given nodes, estimating link strengths, and estimating the most densely interconnected nodes) on two different network visualizations: an adjacency matrix with a heat-map versus a node-link diagram. The results should help shed light on effective methods of visualizing network data for some representative analysis tasks, with the ultimate goal of improving usability and performance for viewers of network data displays.

Dissecting the expression relationships between RNA-binding proteins and their cognate targets in eukaryotic post-transcriptional regulatory networks.

PubMed

Nishtala, Sneha; Neelamraju, Yaseswini; Janga, Sarath Chandra

2016-05-10

RNA-binding proteins (RBPs) are pivotal in orchestrating several steps in the metabolism of RNA in eukaryotes thereby controlling an extensive network of RBP-RNA interactions. Here, we employed CLIP (cross-linking immunoprecipitation)-seq datasets for 60 human RBPs and RIP-ChIP (RNP immunoprecipitation-microarray) data for 69 yeast RBPs to construct a network of genome-wide RBP- target RNA interactions for each RBP. We show in humans that majority (~78%) of the RBPs are strongly associated with their target transcripts at transcript level while ~95% of the studied RBPs were also found to be strongly associated with expression levels of target transcripts when protein expression levels of RBPs were employed. At transcript level, RBP - RNA interaction data for the yeast genome, exhibited a strong association for 63% of the RBPs, confirming the association to be conserved across large phylogenetic distances. Analysis to uncover the features contributing to these associations revealed the number of target transcripts and length of the selected protein-coding transcript of an RBP at the transcript level while intensity of the CLIP signal, number of RNA-Binding domains, location of the binding site on the transcript, to be significant at the protein level. Our analysis will contribute to improved modelling and prediction of post-transcriptional networks.

Dissecting the expression relationships between RNA-binding proteins and their cognate targets in eukaryotic post-transcriptional regulatory networks

NASA Astrophysics Data System (ADS)

Nishtala, Sneha; Neelamraju, Yaseswini; Janga, Sarath Chandra

2016-05-01

RNA-binding proteins (RBPs) are pivotal in orchestrating several steps in the metabolism of RNA in eukaryotes thereby controlling an extensive network of RBP-RNA interactions. Here, we employed CLIP (cross-linking immunoprecipitation)-seq datasets for 60 human RBPs and RIP-ChIP (RNP immunoprecipitation-microarray) data for 69 yeast RBPs to construct a network of genome-wide RBP- target RNA interactions for each RBP. We show in humans that majority (~78%) of the RBPs are strongly associated with their target transcripts at transcript level while ~95% of the studied RBPs were also found to be strongly associated with expression levels of target transcripts when protein expression levels of RBPs were employed. At transcript level, RBP - RNA interaction data for the yeast genome, exhibited a strong association for 63% of the RBPs, confirming the association to be conserved across large phylogenetic distances. Analysis to uncover the features contributing to these associations revealed the number of target transcripts and length of the selected protein-coding transcript of an RBP at the transcript level while intensity of the CLIP signal, number of RNA-Binding domains, location of the binding site on the transcript, to be significant at the protein level. Our analysis will contribute to improved modelling and prediction of post-transcriptional networks.

Mining integrated semantic networks for drug repositioning opportunities

PubMed Central

Mullen, Joseph; Tipney, Hannah

2016-01-01

Current research and development approaches to drug discovery have become less fruitful and more costly. One alternative paradigm is that of drug repositioning. Many marketed examples of repositioned drugs have been identified through serendipitous or rational observations, highlighting the need for more systematic methodologies to tackle the problem. Systems level approaches have the potential to enable the development of novel methods to understand the action of therapeutic compounds, but requires an integrative approach to biological data. Integrated networks can facilitate systems level analyses by combining multiple sources of evidence to provide a rich description of drugs, their targets and their interactions. Classically, such networks can be mined manually where a skilled person is able to identify portions of the graph (semantic subgraphs) that are indicative of relationships between drugs and highlight possible repositioning opportunities. However, this approach is not scalable. Automated approaches are required to systematically mine integrated networks for these subgraphs and bring them to the attention of the user. We introduce a formal framework for the definition of integrated networks and their associated semantic subgraphs for drug interaction analysis and describe DReSMin, an algorithm for mining semantically-rich networks for occurrences of a given semantic subgraph. This algorithm allows instances of complex semantic subgraphs that contain data about putative drug repositioning opportunities to be identified in a computationally tractable fashion, scaling close to linearly with network data. We demonstrate the utility of our approach by mining an integrated drug interaction network built from 11 sources. This work identified and ranked 9,643,061 putative drug-target interactions, showing a strong correlation between highly scored associations and those supported by literature. We discuss the 20 top ranked associations in more detail, of which 14 are novel and 6 are supported by the literature. We also show that our approach better prioritizes known drug-target interactions, than other state-of-the art approaches for predicting such interactions. PMID:26844016

Insights into the Ecology and Evolution of Polyploid Plants through Network Analysis.

PubMed

Gallagher, Joseph P; Grover, Corrinne E; Hu, Guanjing; Wendel, Jonathan F

2016-06-01

Polyploidy is a widespread phenomenon throughout eukaryotes, with important ecological and evolutionary consequences. Although genes operate as components of complex pathways and networks, polyploid changes in genes and gene expression have typically been evaluated as either individual genes or as a part of broad-scale analyses. Network analysis has been fruitful in associating genomic and other 'omic'-based changes with phenotype for many systems. In polyploid species, network analysis has the potential not only to facilitate a better understanding of the complex 'omic' underpinnings of phenotypic and ecological traits common to polyploidy, but also to provide novel insight into the interaction among duplicated genes and genomes. This adds perspective to the global patterns of expression (and other 'omic') change that accompany polyploidy and to the patterns of recruitment and/or loss of genes following polyploidization. While network analysis in polyploid species faces challenges common to other analyses of duplicated genomes, present technologies combined with thoughtful experimental design provide a powerful system to explore polyploid evolution. Here, we demonstrate the utility and potential of network analysis to questions pertaining to polyploidy with an example involving evolution of the transgressively superior cotton fibres found in polyploid Gossypium hirsutum. By combining network analysis with prior knowledge, we provide further insights into the role of profilins in fibre domestication and exemplify the potential for network analysis in polyploid species. © 2016 John Wiley & Sons Ltd.

Qualitative Analysis of Commercial Social Network Profiles

NASA Astrophysics Data System (ADS)

Melendez, Lester; Wolfson, Ouri; Adjouadi, Malek; Rishe, Naphtali

Social-networking sites have become an integral part of many users' daily internet routine. Commercial enterprises have been quick to recognize this and are subsequently creating profiles for many of their products and services. Commercial enterprises use social network profiles to target and interact with potential customers as well as to provide a gateway for users of the product or service to interact with each other. Many commercial enterprises use the statistics from their product or service's social network profile to tout the popularity and success of the product or service being showcased. They will use statistics such as number of friends, number of daily visits, number of interactions, and other similar measurements to quantify their claims. These statistics are often not a clear indication of the true popularity and success of the product. In this chapter the term product is used to refer to any tangible or intangible product, service, celebrity, personality, film, book, or other entity produced by a commercial enterprise.

A quantitative chaperone interaction network reveals the architecture of cellular protein homeostasis pathways

PubMed Central

Taipale, Mikko; Tucker, George; Peng, Jian; Krykbaeva, Irina; Lin, Zhen-Yuan; Larsen, Brett; Choi, Hyungwon; Berger, Bonnie; Gingras, Anne-Claude; Lindquist, Susan

2014-01-01

Chaperones are abundant cellular proteins that promote the folding and function of their substrate proteins (clients). In vivo, chaperones also associate with a large and diverse set of co-factors (co-chaperones) that regulate their specificity and function. However, how these co-chaperones regulate protein folding and whether they have chaperone-independent biological functions is largely unknown. We have combined mass spectrometry and quantitative high-throughput LUMIER assays to systematically characterize the chaperone/co-chaperone/client interaction network in human cells. We uncover hundreds of novel chaperone clients, delineate their participation in specific co-chaperone complexes, and establish a surprisingly distinct network of protein/protein interactions for co-chaperones. As a salient example of the power of such analysis, we establish that NUDC family co-chaperones specifically associate with structurally related but evolutionarily distinct β-propeller folds. We provide a framework for deciphering the proteostasis network, its regulation in development and disease, and expand the use of chaperones as sensors for drug/target engagement. PMID:25036637

Reconstruction of an Immune Dynamic Model to Simulate the Contrasting Role of Auxin and Cytokinin in Plant Immunity.

PubMed

Kaltdorf, Martin; Dandekar, Thomas; Naseem, Muhammad

2017-01-01

In order to increase our understanding of biological dependencies in plant immune signaling pathways, the known interactions involved in plant immune networks are modeled. This allows computational analysis to predict the functions of growth related hormones in plant-pathogen interaction. The SQUAD (Standardized Qualitative Dynamical Systems) algorithm first determines stable system states in the network and then use them to compute continuous dynamical system states. Our reconstructed Boolean model encompassing hormone immune networks of Arabidopsis thaliana (Arabidopsis) and pathogenicity factors injected by model pathogen Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) can be exploited to determine the impact of growth hormones in plant immunity. We describe a detailed working protocol how to use the modified SQUAD-package by exemplifying the contrasting effects of auxin and cytokinins in shaping plant-pathogen interaction.

Integration of structural dynamics and molecular evolution via protein interaction networks: a new era in genomic medicine.

PubMed

Kumar, Avishek; Butler, Brandon M; Kumar, Sudhir; Ozkan, S Banu

2015-12-01

Sequencing technologies are revealing many new non-synonymous single nucleotide variants (nsSNVs) in each personal exome. To assess their functional impacts, comparative genomics is frequently employed to predict if they are benign or not. However, evolutionary analysis alone is insufficient, because it misdiagnoses many disease-associated nsSNVs, such as those at positions involved in protein interfaces, and because evolutionary predictions do not provide mechanistic insights into functional change or loss. Structural analyses can aid in overcoming both of these problems by incorporating conformational dynamics and allostery in nSNV diagnosis. Finally, protein-protein interaction networks using systems-level methodologies shed light onto disease etiology and pathogenesis. Bridging these network approaches with structurally resolved protein interactions and dynamics will advance genomic medicine. Copyright © 2015 Elsevier Ltd. All rights reserved.

Stochastic availability analysis of operational data systems in the Deep Space Network

NASA Technical Reports Server (NTRS)

Issa, T. N.

1991-01-01

Existing availability models of standby redundant systems consider only an operator's performance and its interaction with the hardware performance. In the case of operational data systems in the Deep Space Network (DSN), in addition to an operator system interface, a controller reconfigures the system and links a standby unit into the network data path upon failure of the operating unit. A stochastic (Markovian) process technique is used to model and analyze the availability performance and occurrence of degradation due to partial failures are quantitatively incorporated into the model. Exact expressions of the steady state availability and proportion degraded performance measures are derived for the systems under study. The interaction among the hardware, operator, and controller performance parameters and that interaction's effect on data availability are evaluated and illustrated for an operational data processing system.

Impacts of clustering on interacting epidemics.

PubMed

Wang, Bing; Cao, Lang; Suzuki, Hideyuki; Aihara, Kazuyuki

2012-07-07

Since community structures in real networks play a major role for the epidemic spread, we therefore explore two interacting diseases spreading in networks with community structures. As a network model with community structures, we propose a random clique network model composed of different orders of cliques. We further assume that each disease spreads only through one type of cliques; this assumption corresponds to the issue that two diseases spread inside communities and outside them. Considering the relationship between the susceptible-infected-recovered (SIR) model and the bond percolation theory, we apply this theory to clique random networks under the assumption that the occupation probability is clique-type dependent, which is consistent with the observation that infection rates inside a community and outside it are different, and obtain a number of statistical properties for this model. Two interacting diseases that compete the same hosts are also investigated, which leads to a natural generalization of analyzing an arbitrary number of infectious diseases. For two-disease dynamics, the clustering effect is hypersensitive to the cohesiveness and concentration of cliques; this illustrates the impacts of clustering and the composition of subgraphs in networks on epidemic behavior. The analysis of coexistence/bistability regions provides significant insight into the relationship between the network structure and the potential epidemic prevalence. Copyright © 2012 Elsevier Ltd. All rights reserved.

A geovisual analytic approach to understanding geo-social relationships in the international trade network.

PubMed

Luo, Wei; Yin, Peifeng; Di, Qian; Hardisty, Frank; MacEachren, Alan M

2014-01-01

The world has become a complex set of geo-social systems interconnected by networks, including transportation networks, telecommunications, and the internet. Understanding the interactions between spatial and social relationships within such geo-social systems is a challenge. This research aims to address this challenge through the framework of geovisual analytics. We present the GeoSocialApp which implements traditional network analysis methods in the context of explicitly spatial and social representations. We then apply it to an exploration of international trade networks in terms of the complex interactions between spatial and social relationships. This exploration using the GeoSocialApp helps us develop a two-part hypothesis: international trade network clusters with structural equivalence are strongly 'balkanized' (fragmented) according to the geography of trading partners, and the geographical distance weighted by population within each network cluster has a positive relationship with the development level of countries. In addition to demonstrating the potential of visual analytics to provide insight concerning complex geo-social relationships at a global scale, the research also addresses the challenge of validating insights derived through interactive geovisual analytics. We develop two indicators to quantify the observed patterns, and then use a Monte-Carlo approach to support the hypothesis developed above.

Gene network biological validity based on gene-gene interaction relevance.

PubMed

Gómez-Vela, Francisco; Díaz-Díaz, Norberto

2014-01-01

In recent years, gene networks have become one of the most useful tools for modeling biological processes. Many inference gene network algorithms have been developed as techniques for extracting knowledge from gene expression data. Ensuring the reliability of the inferred gene relationships is a crucial task in any study in order to prove that the algorithms used are precise. Usually, this validation process can be carried out using prior biological knowledge. The metabolic pathways stored in KEGG are one of the most widely used knowledgeable sources for analyzing relationships between genes. This paper introduces a new methodology, GeneNetVal, to assess the biological validity of gene networks based on the relevance of the gene-gene interactions stored in KEGG metabolic pathways. Hence, a complete KEGG pathway conversion into a gene association network and a new matching distance based on gene-gene interaction relevance are proposed. The performance of GeneNetVal was established with three different experiments. Firstly, our proposal is tested in a comparative ROC analysis. Secondly, a randomness study is presented to show the behavior of GeneNetVal when the noise is increased in the input network. Finally, the ability of GeneNetVal to detect biological functionality of the network is shown.

A Geovisual Analytic Approach to Understanding Geo-Social Relationships in the International Trade Network

PubMed Central

Luo, Wei; Yin, Peifeng; Di, Qian; Hardisty, Frank; MacEachren, Alan M.

2014-01-01

The world has become a complex set of geo-social systems interconnected by networks, including transportation networks, telecommunications, and the internet. Understanding the interactions between spatial and social relationships within such geo-social systems is a challenge. This research aims to address this challenge through the framework of geovisual analytics. We present the GeoSocialApp which implements traditional network analysis methods in the context of explicitly spatial and social representations. We then apply it to an exploration of international trade networks in terms of the complex interactions between spatial and social relationships. This exploration using the GeoSocialApp helps us develop a two-part hypothesis: international trade network clusters with structural equivalence are strongly ‘balkanized’ (fragmented) according to the geography of trading partners, and the geographical distance weighted by population within each network cluster has a positive relationship with the development level of countries. In addition to demonstrating the potential of visual analytics to provide insight concerning complex geo-social relationships at a global scale, the research also addresses the challenge of validating insights derived through interactive geovisual analytics. We develop two indicators to quantify the observed patterns, and then use a Monte-Carlo approach to support the hypothesis developed above. PMID:24558409

Privacy Breach Analysis in Social Networks

NASA Astrophysics Data System (ADS)

Nagle, Frank

This chapter addresses various aspects of analyzing privacy breaches in social networks. We first review literature that defines three types of privacy breaches in social networks: interactive, active, and passive. We then survey the various network anonymization schemes that have been constructed to address these privacy breaches. After exploring these breaches and anonymization schemes, we evaluate a measure for determining the level of anonymity inherent in a network graph based on its topological structure. Finally, we close by emphasizing the difficulty of anonymizing social network data while maintaining usability for research purposes and offering areas for future work.

An ANOVA approach for statistical comparisons of brain networks.

PubMed

Fraiman, Daniel; Fraiman, Ricardo

2018-03-16

The study of brain networks has developed extensively over the last couple of decades. By contrast, techniques for the statistical analysis of these networks are less developed. In this paper, we focus on the statistical comparison of brain networks in a nonparametric framework and discuss the associated detection and identification problems. We tested network differences between groups with an analysis of variance (ANOVA) test we developed specifically for networks. We also propose and analyse the behaviour of a new statistical procedure designed to identify different subnetworks. As an example, we show the application of this tool in resting-state fMRI data obtained from the Human Connectome Project. We identify, among other variables, that the amount of sleep the days before the scan is a relevant variable that must be controlled. Finally, we discuss the potential bias in neuroimaging findings that is generated by some behavioural and brain structure variables. Our method can also be applied to other kind of networks such as protein interaction networks, gene networks or social networks.

Disentangling the attention network test: behavioral, event related potentials, and neural source analyses

PubMed Central

Galvao-Carmona, Alejandro; González-Rosa, Javier J.; Hidalgo-Muñoz, Antonio R.; Páramo, Dolores; Benítez, María L.; Izquierdo, Guillermo; Vázquez-Marrufo, Manuel

2014-01-01

Background: The study of the attentional system remains a challenge for current neuroscience. The “Attention Network Test” (ANT) was designed to study simultaneously three different attentional networks (alerting, orienting, and executive) based in subtraction of different experimental conditions. However, some studies recommend caution with these calculations due to the interactions between the attentional networks. In particular, it is highly relevant that several interpretations about attentional impairment have arisen from these calculations in diverse pathologies. Event related potentials (ERPs) and neural source analysis can be applied to disentangle the relationships between these attentional networks not specifically shown by behavioral measures. Results: This study shows that there is a basic level of alerting (tonic alerting) in the no cue (NC) condition, represented by a slow negative trend in the ERP trace prior to the onset of the target stimuli. A progressive increase in the CNV amplitude related to the amount of information provided by the cue conditions is also shown. Neural source analysis reveals specific modulations of the CNV related to a task-related expectancy presented in the NC condition; a late modulation triggered by the central cue (CC) condition and probably representing a generic motor preparation; and an early and late modulation for spatial cue (SC) condition suggesting specific motor and sensory preactivation. Finally, the first component in the information processing of the target stimuli modulated by the interaction between orienting network and the executive system can be represented by N1. Conclusions: The ANT is useful as a paradigm to study specific attentional mechanisms and their interactions. However, calculation of network effects is based in subtractions with non-comparable experimental conditions, as evidenced by the present data, which can induce misinterpretations in the study of the attentional capacity in human subjects. PMID:25352800

Social insect colony as a biological regulatory system: modelling information flow in dominance networks.

PubMed

Nandi, Anjan K; Sumana, Annagiri; Bhattacharya, Kunal

2014-12-06

Social insects provide an excellent platform to investigate flow of information in regulatory systems since their successful social organization is essentially achieved by effective information transfer through complex connectivity patterns among the colony members. Network representation of such behavioural interactions offers a powerful tool for structural as well as dynamical analysis of the underlying regulatory systems. In this paper, we focus on the dominance interaction networks in the tropical social wasp Ropalidia marginata-a species where behavioural observations indicate that such interactions are principally responsible for the transfer of information between individuals about their colony needs, resulting in a regulation of their own activities. Our research reveals that the dominance networks of R. marginata are structurally similar to a class of naturally evolved information processing networks, a fact confirmed also by the predominance of a specific substructure-the 'feed-forward loop'-a key functional component in many other information transfer networks. The dynamical analysis through Boolean modelling confirms that the networks are sufficiently stable under small fluctuations and yet capable of more efficient information transfer compared to their randomized counterparts. Our results suggest the involvement of a common structural design principle in different biological regulatory systems and a possible similarity with respect to the effect of selection on the organization levels of such systems. The findings are also consistent with the hypothesis that dominance behaviour has been shaped by natural selection to co-opt the information transfer process in such social insect species, in addition to its primal function of mediation of reproductive competition in the colony. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Inferring protein domains associated with drug side effects based on drug-target interaction network

PubMed Central

2013-01-01

Background Most phenotypic effects of drugs are involved in the interactions between drugs and their target proteins, however, our knowledge about the molecular mechanism of the drug-target interactions is very limited. One of challenging issues in recent pharmaceutical science is to identify the underlying molecular features which govern drug-target interactions. Results In this paper, we make a systematic analysis of the correlation between drug side effects and protein domains, which we call "pharmacogenomic features," based on the drug-target interaction network. We detect drug side effects and protein domains that appear jointly in known drug-target interactions, which is made possible by using classifiers with sparse models. It is shown that the inferred pharmacogenomic features can be used for predicting potential drug-target interactions. We also discuss advantages and limitations of the pharmacogenomic features, compared with the chemogenomic features that are the associations between drug chemical substructures and protein domains. Conclusion The inferred side effect-domain association network is expected to be useful for estimating common drug side effects for different protein families and characteristic drug side effects for specific protein domains. PMID:24565527

Topology and weights in a protein domain interaction network--a novel way to predict protein interactions.

PubMed

Wuchty, Stefan

2006-05-23

While the analysis of unweighted biological webs as diverse as genetic, protein and metabolic networks allowed spectacular insights in the inner workings of a cell, biological networks are not only determined by their static grid of links. In fact, we expect that the heterogeneity in the utilization of connections has a major impact on the organization of cellular activities as well. We consider a web of interactions between protein domains of the Protein Family database (PFAM), which are weighted by a probability score. We apply metrics that combine the static layout and the weights of the underlying interactions. We observe that unweighted measures as well as their weighted counterparts largely share the same trends in the underlying domain interaction network. However, we only find weak signals that weights and the static grid of interactions are connected entities. Therefore assuming that a protein interaction is governed by a single domain interaction, we observe strong and significant correlations of the highest scoring domain interaction and the confidence of protein interactions in the underlying interactions of yeast and fly. Modeling an interaction between proteins if we find a high scoring protein domain interaction we obtain 1, 428 protein interactions among 361 proteins in the human malaria parasite Plasmodium falciparum. Assessing their quality by a logistic regression method we observe that increasing confidence of predicted interactions is accompanied by high scoring domain interactions and elevated levels of functional similarity and evolutionary conservation. Our results indicate that probability scores are randomly distributed, allowing to treat static grid and weights of domain interactions as separate entities. In particular, these finding confirms earlier observations that a protein interaction is a matter of a single interaction event on domain level. As an immediate application, we show a simple way to predict potential protein interactions by utilizing expectation scores of single domain interactions.

a Model for Brand Competition Within a Social Network

NASA Astrophysics Data System (ADS)

Huerta-Quintanilla, R.; Canto-Lugo, E.; Rodríguez-Achach, M.

An agent-based model was built representing an economic environment in which m brands are competing for a product market. These agents represent companies that interact within a social network in which a certain agent persuades others to update or shift their brands; the brands of the products they are using. Decision rules were established that caused each agent to react according to the economic benefits it would receive; they updated/shifted only if it was beneficial. Each agent can have only one of the m possible brands, and she can interact with its two nearest neighbors and another set of agents which are chosen according to a particular set of rules in the network topology. An absorbing state was always reached in which a single brand monopolized the network (known as condensation). The condensation time varied as a function of model parameters is studied including an analysis of brand competition using different networks.

Transformational leadership and group interaction as climate antecedents: a social network analysis.

PubMed

Zohar, Dov; Tenne-Gazit, Orly

2008-07-01

In order to test the social mechanisms through which organizational climate emerges, this article introduces a model that combines transformational leadership and social interaction as antecedents of climate strength (i.e., the degree of within-unit agreement about climate perceptions). Despite their longstanding status as primary variables, both antecedents have received limited empirical research. The sample consisted of 45 platoons of infantry soldiers from 5 different brigades, using safety climate as the exemplar. Results indicate a partially mediated model between transformational leadership and climate strength, with density of group communication network as the mediating variable. In addition, the results showed independent effects for group centralization of the communication and friendship networks, which exerted incremental effects on climate strength over transformational leadership. Whereas centralization of the communication network was found to be negatively related to climate strength, centralization of the friendship network was positively related to it. Theoretical and practical implications are discussed.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sunden, Fanny; Peck, Ariana; Salzman, Julia

Enzymes enable life by accelerating reaction rates to biological timescales. Conventional studies have focused on identifying the residues that have a direct involvement in an enzymatic reaction, but these so-called ‘catalytic residues’ are embedded in extensive interaction networks. Although fundamental to our understanding of enzyme function, evolution, and engineering, the properties of these networks have yet to be quantitatively and systematically explored. We dissected an interaction network of five residues in the active site of Escherichia coli alkaline phosphatase. Analysis of the complex catalytic interdependence of specific residues identified three energetically independent but structurally interconnected functional units with distinct modesmore » of cooperativity. From an evolutionary perspective, this network is orders of magnitude more probable to arise than a fully cooperative network. From a functional perspective, new catalytic insights emerge. Further, such comprehensive energetic characterization will be necessary to benchmark the algorithms required to rationally engineer highly efficient enzymes.« less